Ethyl Acetate → allyl (1R,5S,6S)-2-[(2R, 4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 1755720ノート

反応式

HRID 1755720 の反応式
C(N(CC)C(C)C)(C)C.O(P(O[C:27]1[C@H:28]([CH3:44])[C@H:29]2[C@@H:39]([C@H:40]([OH:42])[CH3:41])[C:38](=[O:43])[N:30]2[C:31]=1[C:32]([O:34][CH2:35][CH:36]=[CH2:37])=[O:33])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH2:45]([O:48][C:49]([N:51]1[CH2:55][C@@H:54]([SH:56])[CH2:53][C@H:52]1[CH2:57][CH:58]1[CH2:62][CH2:61][NH:60][C:59]1=[O:63])=[O:50])[CH:46]=[CH2:47].C(OCC)(=O)C>C(#N)C>[CH2:45]([O:48][C:49]([N:51]1[CH2:55][C@@H:54]([S:56][C:27]2[C@H:28]([CH3:44])[C@@H:29]3[C@@H:39]([C@H:40]([OH:42])[CH3:41])[C:38](=[O:43])[N:30]3[C:31]=2[C:32]([O:34][CH2:35][CH:36]=[CH2:37])=[O:33])[CH2:53][C@H:52]1[CH2:57][CH:58]1[CH2:62][CH2:61][NH:60][C:59]1=[O:63])=[O:50])[CH:46]=[CH2:47]

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 18657843(2R,4S)-N-allyloxycarbonyl-4-mercapto-2-(2-pyrrolidon-3ylmethyl)pyrrolidineHCID 57175810allyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

生成物 1

HCID 57051347allyl (1R,5S,6S)-2-[(2R, 4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate収率 51.8%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
5 °C

実験手順

N,N-diisopropylethylamine (0.26 ml, 1.52 mmol) was dropwise added to a solution of allyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (759 mg, 1.52 mmol) and (2R,4S)-N-allyloxycarbonyl-4-mercapto-2-(2-pyrrolidon-3-ylmethyl)pyrrolidine (432 mg, 1.52 mmol) in acetonitrile (11 ml) at -40° C. The reaction solution mixture was stirred at the same temperature for 3 hours and further at 5° C. for 16 hours. Ethyl acetate (60 ml) was added to the reaction solution. This solution mixture was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel flash column chromatography (Wakogel™ C-300, 40 ml, acetone-ethyl acetate 2:3), and the fraction containing the desired product was concentrated to obtain allyl (1R,5S,6S)-2-[(2R, 4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (420 mg, yield: 51.8%) in the form of foam.

後処理

  1. washThis solution mixture was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution
  2. dry with materiala saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel flash column chromatography (Wakogel™ C-300, 40 ml, acetone-ethyl acetate 2:3)
  5. additionthe fraction containing the desired product
  6. concentrationwas concentrated

出典と根拠

ORDレコード
ord-76b9f3ed2be3498a8320ae98e4df9f67
出典データセット
uspto-grants-1995_08
特許番号
US05438054

反応ノート

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