Phosphate → (1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester

HRID 36497

反応式

HRID 36497 の反応式
C([C@H:5]([O:27][SiH:28]([CH3:30])[CH3:29])[C@H:6]1[C:13](=[O:14])[N:12]2[C@@H:7]1[C@@H:8]([CH3:26])[C:9](=O)[S:10][CH:11]2[C:15]([O:17][CH2:18][O:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])=[O:16])(C)(C)C.[C:31]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:50][C:51]([CH3:54])([O-])[CH3:52].[K+].P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.S[C@@H:74]1[CH2:78][NH:77][C:76](=[S:79])[CH2:75]1.C(N(C(C)C)CC)(C)C.P([O-])([O-])([O-])=O>C1(C)C=CC=CC=1.C(#N)C>[Si:28]([O:27][C@@H:5]([C@H:6]1[C:13](=[O:14])[N:12]2[C:11]([C:15]([O:17][CH2:18][O:19][C:20](=[O:24])[CH:21]([CH3:22])[CH3:23])=[O:16])=[C:9]([S:10][C@H:74]3[CH2:78][NH:77][C:76](=[S:79])[CH2:75]3)[C@H:8]([CH3:26])[C@H:7]12)[CH3:31])([C:51]([CH3:54])([CH3:52])[CH3:50])([CH3:30])[CH3:29]

参加物

10

反応物 7

HCID 1061PhosphateHCID 11776TriphenylphosphineHCID 75654Diphenyl chlorophosphateHCID 81531DiisopropylethylamineHCID 11051701(4S)-4-mercaptopyrrolidin-2-thioneHCID 23665647Potassium tert-butoxideHCID 131718995isobutyryloxymethyl (5R,6S,7S)-7-[(R)-1-tert-butyldimethylsilyloxymethyl]-5-methyl-4,8-dioxo-1-aza-3-thia-bicyclo-[4.2.0]octan-2-carboxylate

生成物 1

HCID 11103665(1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester収率 42.2%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
-40 °C

実験手順

In 10 ml of toluene were dissolved 500 mg of isobutyryloxymethyl (5R,6S,7S)-7-[(R)-1-tert-butyldimethylsilyloxymethyl]-5-methyl-4,8-dioxo-1-aza-3-thia-bicyclo-[4.2.0]octan-2-carboxylate and 277 mg of triphenylphosphine, 130 mg of potassium tert-butoxide was added thereto under nitrogen gas at -40° C. while stirring, and the mixture was stirred at the same temperature for 50 minutes. To the reaction mixture was added dropwise 10 ml of acetonitrile solution containing 312 mg of diphenyl chlorophosphate at -40° C., and the mixture was stirred for 40 minutes. To the reaction mixture were added 155 mg of (4S)-4-mercaptopyrrolidin-2-thione and 148 mg of diisopropylethylamine, and the mixture was stirred at -20° C. for 80 minutes, and then at -5° C. for 1.5 hours. The reaction mixture was poured into a 0.1M phosphate buffer (pH 7.0) and extracted with ethyl acetate. After the extract was washed and dried, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate:chloroform=5:5:1) to obtain 248 mg of isobutyryloxymethyl (1R,5S,6S)-6-[(R)-1-tert-butyldimethylsilyloxyethyl]-2-[(4R)-pyrrolidin-2-thion-4-ylthio]-1-methylcarbapen-2-em-3-carboxylate.

後処理

  1. additionwas added
  2. stirringthe mixture was stirred at the same temperature for 50 minutes
  3. stirringthe mixture was stirred for 40 minutes
  4. stirringthe mixture was stirred at -20° C. for 80 minutes
  5. extractionextracted with ethyl acetate
  6. washAfter the extract was washed
  7. customdried
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate:chloroform=5:5:1)

出典と根拠

ORDレコード
ord-aecf9b53f27947c0b6ec1f7fbcb48698
出典データセット
uspto-grants-1995_05
特許番号
US05414081

関連ノート

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