• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:

    公开号:SU731892A3
    申请号:SU742079382
    申请日:1974-12-02
    公开日:1980-04-30
    发明作者:Стендиш Ноулес Уильям；Джером Сабаки Милтон；Дэйл Вайнъярд Билли
    申请人:Монсанто Компани (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to an improved process for the preparation of optical isomers of P - substituted with nyh-ot-a-cilamido propionic acids of the general formula: P-slg-cn-oon No. 1-SOSH5 where R is phenyl, 3-methoxy-4-acetoxyphenyl or N-acetylindolyl . L - the antipode of such phenylalanines is particularly desirable. For example, 3- (3,4-dioxyphenyl) -b-alanine (L-DOPA) has proven to be useful in the treatment of sympto MY Parkinson's disease. Similarly, Jj-Phenylalanine is used as an intermediate in the preparation of L-aspargyl-L-phenylalanine alkyl esters, which are synthetic sweet substances. The known method of obtaining pticic isomers 1 by asymmetric hydrogenation of acrylic acid derivatives with hydrogen in the presence of a rhodium catalyst at 25–50 s and pressure up to 2 atm. However, according to this method, the yield of the target product and their optical purities are not high. The purpose of the invention is to increase the yield of the product. The goal is achieved by the described method of obtaining f5 -substituted-o-acylamidopropionic acids of the general formula B-CHg-CH-COOH TSH-COCH3 where R is phenyl, 3-methoxy-4-acetoxyphenyl or N-acetylindolyl, by hydrogenating with the corresponding p-substituted ot-acylamido acrylic acid in the presence of a rhodium catalyst at 25-5b ° C and a pressure of up to 2 atm, which means that the hydrogenation is carried out at a pressure of 2.8-27 atm in the presence of a rhodium catalyst containing a bisphosphine ligand of the general formula where R tl is methoxyphenyl, n - x Orfenov, p - dimethylaminophenyl, cyclohexyl, ethyl or phenyl.
    Distinctive features of the method are to conduct the hydrogenation reaction at a pressure of 2.8-27 atm in the presence of a rhodium catalyst containing a bisphosphine ligand.
    The process technology is as follows: p-substituted-1-acylamido acrylic acid, a rhodium catalyst containing a bisphosphine ligand is placed in a reactor and hydrogenation is carried out with hydrogen at a pressure of 2.8-27 atm at 2550 s.
    The hydrogenation is usually carried out in solvents such as methanol or isopropanol. The concentration of the catalyst is usually 0.001-5 wt.% Metal, based on the acid being hydrogenated. Hydrogenation can be carried out in the presence of a base, such as caustic soda.
    In the examples, the percentage optical purity is determined, and the optical activity expressed as specific rotations is measured in the same solvent: Observed optical activity
    Optical blends
    Optical activity - J-f frequency,% of pure optical isomer
    Example 1. A solution is prepared from 0.013 g of bis- (cyclooctadiene-1.5) -dichlorodorodi iRh (COD) and 0.024 g of 1,2-bis- (o-anisylphenylphosphino) -ethane, in 5 ml of methanol, by stirring for 15. min at 25 ° C. In the absence of air, 0.5 ml of the solution is added to the sludge from 1.00 g of CX-acetamidopaic acid in 25 ml of 88% isopropanol at. I apply a pressure of 3.5 bar (absolute pressure) of hydrogen to the resulting mass. The hydrogenation reaction is completed within 0.7 hours. An analysis of the reaction mixture indicates that an optical purity of 92.8% of the L-isomer has been achieved.
    Example 2. A solution is blown out of 100.0 g of oC-acetamide-brown acid of brown acid in 100 ml of methanol, 81.5 liters of water and 37.0 g of 50% sodium hydroxide in order to remove oxygen. Then, at and under pressure of 2.87 atm of hydrogen, a catalytic solution is injected consisting of 0.0368 g of cyclooctadiene-1, 2-bis- (0-anisylphenylphosphino) -ethane - rhodium tetrafluoroborate into 2 ml of methanol through a septum. The hydrogenation is completed after 9 hours, resulting in an optical purity of 95-96%. The product is isolated from its sodium salt by adding 45.7 g of 37% NSC. 94.0 g of L-acetyl-b-phenylalanine are obtained; oL + +47.1 (with 1 in 95% ethanol).
    Example 3. Other hydrogenation reactions are carried out using procedures similar to the methods described in MonCiM 1 and 2 procedures. All hydrogenations were carried out with 0.05% rhodium concentrations, based on the weight of the olefin being hydrogenated. The obtained 5 results are presented in the table.
    Example 4. 0.01181 g of 1,2-bis- (o-anisylethylphosphino) -ethane and 0.0193 g of rhodium- (cyclo-Thadien-1.5) -acetyl acetonate are dissolved in 5 ml
    0 C:% 0f Hydrogenated with 1 g of β-acetamidocoric acid, 12.5 ml of СНаОН 8.96 ml of NaOH, 3.5 ml and 0.55 ml of the above solution of catipisator at a pressure of 3.15 atm H2 at 50 s.
    . Hydrogenation is completed after 1/2 hour. The resulting optical purity is 59% (0.785 g H-acetyl-b-phenylalanine and 0.250 g L-acetyl-O-phenylalanine).
    Example 5. 0.0099 g of 1,2-bis- (0-anisylcyclohexyl-esfino) -eta0 and 0.0065 g of rhodium- (cyclooctadiene-1, 5) -acetylacetonate are dissolved in 2 ml of CH, OH.
    1 g of ot-acetamidocoric acid, 20 ml and 0, 5 ml are hydrogenated.
    5 of the specified catalyst solution at a pressure of 2.8 atm. And so on. Hydrogenation was completed after 1 hour. The resulting optical purity (0.809 g N-acetyl-L-phenylalanine and
    Q 0.191 N-acetyl-O-phenylalanine).
    Example 6. 0.0109 g of 1,2bis-o-anisyl- (p-methoxyphenyl) phosphino-ethane; 0.0065 g of rhodium- (cyclooctadiene-1, 5) -acetylacetonate is dissolved in 2 ml of CH, OH.
    one). I g is hydrated with oC-acetamide-boric acid, 20 ml and 0.5 ml of this solution catalyzate at a pressure of 2.8 atm Hg, at 2 5 ° C.
    0 Hydrogenation completed after 3 hours.
    with an optical purity of 85.7% (0.9285 g of K-acetyl-b-phenylalanine and 0.0715 N-acetyl-O-phenylalanine).
    5 2) Hydrate with 1 g of od-acetamidocoric acid, 12.5 ml of CH, OH 8.84 ml of NaOH, 3.36 ml and 0.5 ml of the indicated catalyst solution at a pressure of 3.5 atm. 25 ° C.
    0 The resulting optical purity of 92.8% (0.964 g of s-acetyl-b-phenylalanine and 0.036 g of N-acetyl-D-phenyl-alanine).
    Example 7. 0.0114 g of 1.25-bis p-anisyl- (m-chlorophenyl) phosphono-ethane and 0.0067 g of rhodium- (cyclooctadiene-1, 5) -acetylacetonate are dissolved in 2 ml of SNOH.
    1) Hydrogenating 1 ga-acetamidocoric acid, 25 ml and 0.46 ml 0 of the indicated catalyst solution at a pressure of 3.15 atm H2. at 50 ° c. The resulting optical purity was 96.7% (0.9835 g M-acetyl-b-phenylalanine and 0.0165 g L-acetyl-O-phenyl 5 Nina).
    2) Hydrogenate with 1 g / -acetamidocoric acid, 8.9 ml of NaOH, 12.5 ml, 3 ml and 0.45 ml of the indicated catalyst solution at a pressure of 3.15 atm H2 at. Hydrogenation was completed after 1.3 hours and the resulting optical purity of 94.8%
    (0.974 g L-acetyl-L-phenylalanine and 0.026 g L-acetyl-O-phenylalanine). Pr and measures 8. 0.0166 g of 1,2-bis-o-anionyl- (p-dimethylaminophenyl) phosphino-ethane 0.0066 g of rhodium {- (cyclooctadiene-1, 5) -acetylacetonate is dissolved in 2 ml isopropanol.
    Hydrogenated with 1 g of acetamidocoric acid, 25 ml of isopropane and 0.5 ml of the above catalyst solution at a hydrogen pressure of 3.15 atm at. Hydrogenation was completed after 1/2 hour and the resulting optical purity of 71.6% (0.858 g of K-acetyl-b-phenylalanine and 0.142 g of K-acetyl-B-phenylalanine).
    Methanol 50 Acetate-3-methoxy-4-hydroxy-e-acetamidocoric acid (a) Methanol 50 Acetate-3-methoxy-4-hydroxy-c-acetamidocoric acid (c) Methanol Acetate-3-methoxy-4-hydroxy-c6 - acetamidocoric acid (c) 88% 2-50 Acetate-3-methoxy-4-oxy-o - acetates-propadoric acid (c) 88% 2c {.-Ay; ethamidocoric acid (b) -propanol 88% 2-b Acetamidocoric acid (B) -prop; NOL 88% 2 (.-Adetamido-propacoric acid (c) 50% me- 25 oL-Acetamidocorichtanol (c) on acid (c) 50% meta- 50 ci.-Acetate amido cinniche NOL (c) on acid (B) c /, - Acetamidocoric 50% metha- 50 NOL (c) acid (c)
    - D acetic acid amido-acrylic acid (c) P
    权利要求:
    Claims (1)
    [1]
    1. Canadian patent 937573, cl. 260-314, publ. 1973 (prototype). a) the catalyst of example 1; c) the catalyst from example 2; c) the reaction is carried out in the presence of 0.95 equivalents of caustic soda, based on the acrylic acid present; (d) All optical readings were measured without dilution to volume by comparison with the control, and pure L-acetyl-L-phenylalanine oL p + 47.5 (in 95% ethanol) was used; L-acetyl 3- (4-hydroxy-3-methoxyphenyl) -L-alanine acetate; 40.8 ° (in SNLON) and 3- (L-acetylindolyl) -H-acetyl-L-alanine ti ° - 2035.1 (, 5 in SNdON).
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    引用文献:
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    US3849480A|1968-09-09|1974-11-19|Monsanto Co|Catalytic asymmetric hydrogenation|
    US3855323A|1970-10-14|1974-12-17|Sun Ventures Inc|Olefin isomerization catalysts and process|
    FR2116905A5|1970-12-10|1972-07-21|Inst Francais Du Petrole|NEW BIDENT COORDINATES, THEIR MANUFACTURING AND THEIR APPLICATIONS|
    US3939188A|1972-03-24|1976-02-17|Exxon Research And Engineering Company|Preparation of zerovalent phosphine substituted rhodium compounds and their use in the selective carbonylation of olefins|
    US4008281A|1973-12-03|1977-02-15|Monsanto Company|Asymmetric catalysis|FR2428021B1|1978-06-05|1984-05-25|Kuraray Co|
    JPS55501178A|1979-02-12|1980-12-25|
    JPH0142959B2|1984-03-22|1989-09-18|Takasago Perfumery Co Ltd|
    DE3616057A1|1986-05-13|1987-11-19|Ruhrchemie Ag|METHOD FOR PRODUCING ALDEHYDES|
    US4939288A|1989-01-23|1990-07-03|Monsanto Company|Method of preparing -succinic acid derivatives|
    US5198561A|1989-06-22|1993-03-30|Monsanto Company|Ruthenium-BINAP asymmetric hydrogenation catalyst|
    US5202474A|1989-06-22|1993-04-13|Monsanto Company|Asymmetric catalytic hydrogenation of α-arylpropenoic acids|
    US5233084A|1989-06-22|1993-08-03|Monsanto Company|Method for preparing α-arylpropionic acids|
    US5321153A|1992-06-15|1994-06-14|Monsanto Company|Process for making chiral alpha-amino phosphonates selected novel chiral alpha-amino phosphonates|
    JPH07206768A|1994-01-12|1995-08-08|Nippon Oil Co Ltd|Optically active succinic acid or its derivative|
    WO1997013763A1|1995-10-13|1997-04-17|The Penn State Research Foundation|Asymmetric synthesis catalyzed by transition metal complexes with new chiral ligands|
    GB0004297D0|2000-02-23|2000-04-12|Ucb Sa|2-oxo-1 pyrrolidine derivatives process for preparing them and their uses|
    ES2337826T3|2005-03-17|2010-04-29|Basf Se|METHOD FOR THE PRODUCTION OF OPTICALLY ACTIVE DERIVATIVES OF 3-PHENYLPROPIONIC ACID AND REACTION PRODUCTS OF THE SAME.|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/514,987|US4008281A|1973-12-03|1974-10-15|Asymmetric catalysis|
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