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

HRID 257288Notes

Reaction equation

HRID 257288 reaction equation
[C:1]([O:6][CH2:7][O:8][C:9]([C:11]1[N:15]2[C:16](=[O:28])[C@H:17]([C@H:18]([O:20][Si](C(C)(C)C)(C)C)[CH3:19])[C@H:14]2[C@@H:13]([CH3:29])[C:12]=1[S:30][C@H:31]1[CH2:35][NH:34][C:33](=[S:36])[CH2:32]1)=[O:10])(=[O:5])[CH:2]([CH3:4])[CH3:3].CN(C)C=O.F.[NH4+].P([O-])([O-])([O-])=O>CN1CCCC1=O>[C:1]([O:6][CH2:7][O:8][C:9]([C:11]1[N:15]2[C:16](=[O:28])[C@H:17]([C@H:18]([OH:20])[CH3:19])[C@H:14]2[C@@H:13]([CH3:29])[C:12]=1[S:30][C@H:31]1[CH2:35][NH:34][C:33](=[S:36])[CH2:32]1)=[O:10])(=[O:5])[CH:2]([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 1061PhosphateHCID 6228DimethylformamideHCID 11103665(1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl esterHCID 13685747Ammonium hydrogenfluoride

Product 1

HCID 9955020(1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of (1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester (3 g), dimethylformamide (20 ml), N-methylpyrrolidone (7 ml) and ammonium hydrogenfluoride (1.21 g) is stirred at 20° C. for three days. The reaction mixture is poured into a phosphate buffer (pH 7.0), and the mixture is extracted with ethyl acetate. The aqueous layer is extracted with ethyl acetate, and the organic layers are combined, washed with water, dried, and concentrated under reduced pressure. The resulting residue is crystallized from a mixture of ethyl acetate and diisopropyl ether. To the resultant is added diisopropyl ether, and the precipitate is collected by filtration, and washed to give (1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester (2.17 g) as crystals.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. extractionThe aqueous layer is extracted with ethyl acetate
  3. washwashed with water
  4. customdried
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is crystallized from a mixture of ethyl acetate and diisopropyl ether
  7. additionTo the resultant is added diisopropyl ether
  8. filtrationthe precipitate is collected by filtration
  9. washwashed

Sources & evidence

ORD record
ord-d15255eae5ed479dbac0768ff8dfab88
Source dataset
uspto-grants-1993_11
Patent number
US05260438

Reaction notes

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