• 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:
    7-Alkoxy-3-chloromethyl-3-cephems are provided by reacting a 3-methylenecepham with an alkali metal salt of a lower primary alcohol in the presence of tert-butyl hypochlorite at a temperature ranging from about -80 DEG to about 0 DEG C. The 3-chloromethylcephems provided by this invention are useful intermediates for the preparation of known cephalosporin antibiotics.
    公开号:SU845790A3
    申请号:SU772462783
    申请日:1977-03-21
    公开日:1981-07-07
    发明作者:Аллен Коппел Гари
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    This goal is achieved by the proposed method for the preparation of compounds of general formula 1, which consists in the fact that a 3-methylene cephamic compound of general formula II
    H -R2CONH j-fS
    ,
    where R and R have the indicated meanings are reacted with 1-5 equivalents of alkali metal methylate in the presence of 1-5 equivalents of t-butyl hypochlorite. in an inert organic solvent at a temperature of from -80 to -40 C.
    7-Alkoxy-3-chloromethyl cephalone 1 can be converted into other 3- {substituted methyl) -dephem compounds by nucleophilic substitution of chlorine, in particular into 3-heteroarylthiomethyl cephem compounds. The 7-alkoxy-3-chloromethyl cepheme compounds of Formula 1 are also intermediate products for the preparation of clinically known cephem antibiotics. For example, benzhydryl-7- (2-thienylacetamido) -7-methoxy-3-chlorometh-1-3-cephem-4-carboxylate can be reacted with calcium carbamate followed by removal of the ester group to obtain the well-known antibiotic cefoxitin.
    In the following examples, the spectra of nuclear magnetic resonance were obtained on a T-60 spectrometer using tetramethylsilane as a standard. Chemical shifts are expressed in cG values in parts per million (million) and coupling constants (Y) are expressed in cycles per second.
    Example 1. Benzhydryl-7- (2-thienylacetamido) -7-methoxy-3-chloromethyl-3-cephem-4-carboxylate.
    To a solution of 2 ml of 1.85 M lithium methylate in 25 ml of tetrahydrofuran was added 2 ml of metaiol. The mixture is cooled to a dry bath consisting of ice and acetone, and 0.15 m of tert-butyl hypochlorite is added. A solution of 0.504 g of benzhydryl 7- (2-thienylacetamido) -3-methylene cephamide-4-carboxylate in 4 ml of tetrahydrofuran is then added. After 20 minutes, 3 ml of acetic acid was added at -80 ° C and then the mixture was allowed to warm to 0 ° C. The reaction mixture is evaporated to dryness in vacuo; the residue thus obtained is dissolved in methylene chloride. The methylene chloride solution is thoroughly washed with 5% hydrochloric acid, water and a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and evaporated to dryness in vacuo to GET the indicated product.
    NMR (CDCl ,,),: 3.38 (bs, 2,), 3.46 (55.3, C.-OCHj), 3.82 (s, 2, side chain CHj), 4.34 {s , 2, C2, - CHnCl), 5.04 (s, - l,) and 6.8-7.6 (ArN).
    Example 2. 4-Nitrobenzyl-7-phenoxy-acetamido-7-methoxy-3-chloropyl. Methyl-3-cephem-4-carboxylate.
    This product is prepared from 4-nitrobenzyl-7-phenoxyacetamido-3-methylene cephamide-4-carboxylate in accordance with the process described in Example 1.
    NMR. (SOSTS); sJ: 3.52 (s, 5, C —OCHq, and., 4.52 (m, 2, C —CHfjCO 4.61 5, 2,. side chain CH2), 5.10
    (s, 1, С {, - Э), 5.37 (s, 2, ether СН ,,) and 6.9-8.2 (ArH).
    权利要求:
    Claims (2)
    [1]
    Invention Formula
    The method of obtaining 7-methoxy-3-chloromethyl cephemes of the general formula
    donkey
    : R2C01JH -T XjA
    COOBi
    where R. is benzhydryl or 4-nitrobenzyl; Rn is phenoxymethyl or 2-thienylmethyl, characterized in that.
    in order to simplify the process technology, the 3-methylene cephalic compound of the total formula
    H
    I
    B2 O H- | -j x Wy CH,
    (Joobi
    where R and R "have the indicated meanings, are reacted with 1-5 equivalents of alkali metal methoxide in the presence of i-5 equivalents58457906
    tapes tert.-butyl hypochlorite in the inert- 1. US patent No. 3867378, a nominal organic solvent with cl. 260-243 C, published, 1975 (temperature from -BO to .Type).
    Information sources,
    [2]
    2. US Patent fr 3897424,
    taken into account in the examination of cl. C, publish. 1975.
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    同族专利:
    公开号 | 公开日
    CA1109459A|1981-09-22|
    NL7703061A|1977-09-26|
    DE2712047C2|1985-09-19|
    YU68477A|1982-06-30|
    PT66318A|1977-04-01|
    DK123177A|1977-09-23|
    US4048163A|1977-09-13|
    SE428801B|1983-07-25|
    CS194795B2|1979-12-31|
    NZ183309A|1978-07-28|
    BG27755A3|1979-12-12|
    PH12938A|1979-10-18|
    HU176659B|1981-04-28|
    AR228336A1|1983-02-28|
    DK148261B|1985-05-20|
    GB1573026A|1980-08-13|
    IE44600L|1977-09-22|
    ES457059A1|1978-06-01|
    GR66423B|1981-03-20|
    SE7702736L|1977-09-23|
    AT351676B|1979-08-10|
    BE852670A|1977-09-19|
    JPS52113996A|1977-09-24|
    AU2219977A|1978-08-17|
    AU505101B2|1979-11-08|
    IL51433A|1979-11-30|
    MX4449E|1982-05-11|
    JPS613353B2|1986-01-31|
    PL108101B1|1980-03-31|
    DD129915A5|1978-02-15|
    CH632515A5|1982-10-15|
    ZA77714B|1978-09-27|
    PT66318B|1978-08-14|
    RO70052A|1980-07-15|
    DE2712047A1|1977-09-29|
    ATA194677A|1979-01-15|
    IE44600B1|1982-01-27|
    IL51433D0|1977-04-29|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    GB1241657A|1967-08-21|1971-08-04|Glaxo Lab Ltd|Improvements in or relating to cephalosporin compounds|
    US3637678A|1969-01-13|1972-01-25|Lilly Co Eli|Delta-2 cephalosporin compounds|
    US3705897A|1970-07-07|1972-12-12|Lilly Co Eli|Method for converting delta2 cephalosporin to delta3 cephalosporin|
    BE794554A|1972-01-31|1973-07-26|Lilly Co Eli|NEW DERIVATIVES OF PENICILLIN AND CEPHALUSPORIN|
    US3883518A|1972-05-15|1975-05-13|Merck & Co Inc|3-Methylene cephalosporins|JPS62242730A|1986-04-14|1987-10-23|Mitsubishi Electric Corp|Hot water heater device|
    JPH0341738B2|1986-04-24|1991-06-25|
    KR20020017380A|2000-08-30|2002-03-07|구자홍|Apparatus for controlling capstan motor of tvcr|
    CN107118224B|2017-06-15|2019-09-17|浙江新和成股份有限公司|A kind of preparation method of oxygen cephalosporin nucleus intermediate, its solvated compounds and preparation method thereof|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/669,368|US4048163A|1976-03-22|1976-03-22|Process for preparation of 7-alkoxy-3-chloromethylcephems|
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