تفاعل #552520

ord-655a9d6838a245449c15fbc7ea564b3b

معادلة التفاعل

O=P([O-])([O-])[O-]
phosphate
CN1C[C@H](S)CC1=S
(4R)-N-methyl-4- mercaptopyrrolidine-2-thione
CCN(C(C)C)C(C)C
diisopropylethylamine
CCN(C(C)C)C(C)C
diisopropylethylamine
O=P(Cl)(c1ccccc1)c1ccccc1
diphenylphosphoryl chloride
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2- oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CC(=S)N(C)C3)[C@H](C)[C@H]12
(1R, 5S, 6S)-2-[(4R)-N-methyl- pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen -2-em-3-carboxylic acid 4-nitrobenzyl ester
المردود 68.7%

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.STIRRINGAfter stirring the mixture at 0° C. for 1.5 hour
  2. 2
    أخرىThe precipitated crystal is separated by filtration
  3. 3
    workup.DISSOLUTIONdissolved in a mixture of chloroform (2 liters) and tetrahydrofuran (1 liter)
  4. 4
    غسيلthe solution is washed with water
  5. 5
    أخرىdried
  6. 6
    تركيزconcentrated to dryness under reduced pressure
  7. 7
    أخرىThe residue is crystallized from diethyl ether

الإجراء التجريبي

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2- oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester (25.2 g) is dissolved in anhydrous acetonitrile (173 ml), and thereto are added dropwise diisopropylethylamine (13 ml) and diphenylphosphoryl chloride (15.5 ml) in this order under nitrogen gas below 0° C. After stirring the mixture at the same temperature for 30 minutes, a solution of (4R)-N-methyl-4- mercaptopyrrolidine-2-thione (13 g) and diisopropylethylamine (11.5 g) in anhydrous acetonitrile (173 ml) is added dropwise to the reaction mixture below -5° C. After stirring the mixture at 0° C. for 1.5 hour, the reaction mixture is poured into phosphate buffer (pH 7.0, one liter). The precipitated crystal is separated by filtration and dissolved in a mixture of chloroform (2 liters) and tetrahydrofuran (1 liter), and the solution is washed with water, dried and concentrated to dryness under reduced pressure. The residue is crystallized from diethyl ether to give (1R, 5S, 6S)-2-[(4R)-N-methyl- pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen -2-em-3-carboxylic acid 4-nitrobenzyl ester (23.5 g) as colorless needles.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US05153187uspto-grants-1992_10