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

Reaktionsgleichung

Reaktionsgleichung von HRID 36497
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]

Komponenten

10

Edukt 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

Produkt 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 esterAusbeute 42,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
-40 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-aecf9b53f27947c0b6ec1f7fbcb48698
Quelldatensatz
uspto-grants-1995_05
Patentnummer
US05414081

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