Water → (1R,5S,6S)-6-((1R)-1-Hydroxyethyl)-2-[(3S,5R)-5-(imidazo[5,1-b]thiazol-3-yl)methylpyrrolidin-3-yl]thio-1-methylcarbapen-2-em-3-carboxylic acid

HRID 568237Notes

Reaction equation

HRID 568237 reaction equation
C(OC([N:7]1[C@H:11]([CH2:12][C:13]2[N:14]3[CH:20]=[N:19][CH:18]=[C:15]3[S:16][CH:17]=2)[CH2:10][C@H:9]([S:21][C:22]2[C@H:23]([CH3:39])[C@@H:24]3[C@@H:34]([C@H:35]([OH:37])[CH3:36])[C:33](=[O:38])[N:25]3[C:26]=2[C:27]([O:29]CC=C)=[O:28])[CH2:8]1)=O)C=C.CNC1C=CC=CC=1.O.C(OCC)(=O)C>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:37][C@@H:35]([C@H:34]1[C:33](=[O:38])[N:25]2[C:26]([C:27]([OH:29])=[O:28])=[C:22]([S:21][C@H:9]3[CH2:10][C@@H:11]([CH2:12][C:13]4[N:14]5[CH:20]=[N:19][CH:18]=[C:15]5[S:16][CH:17]=4)[NH:7][CH2:8]3)[C@H:23]([CH3:39])[C@H:24]12)[CH3:36]

Participants

7

Reactant 4

HCID 962WaterHCID 7515N-MethylanilineHCID 8857Ethyl AcetateHCID 131722327allyl(1R,5S,6S)-2-[(3S,5R)-1-allyloxycarbonyl-5-(imidazo[5,1-b]thiazol-3-yl)methylpyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131722326(1R,5S,6S)-6-((1R)-1-Hydroxyethyl)-2-[(3S,5R)-5-(imidazo[5,1-b]thiazol-3-yl)methylpyrrolidin-3-yl]thio-1-methylcarbapen-2-em-3-carboxylic acidYield 11%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

Tetrakis(triphenylphosphine)palladium(0) (14.3 mg) is added to a solution of 71 mg of allyl(1R,5S,6S)-2-[(3S,5R)-1-allyloxycarbonyl-5-(imidazo[5,1-b]thiazol-3-yl)methylpyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate and 0.08 ml of N-methylaniline in 1.0 ml of dry dichloromethane, and the mixture is stirred in an argon atmosphere at room temperature for 40 min. Distilled water (3 ml) and 5 ml of ethyl acetate are added thereto to remove insolubles, followed by washing twice with 5 ml of ethyl acetate and concentration under reduced pressure. The concentrate is then freeze dried to give a colorless flocculent material. This material is then purified by column chromatography on Cosmosil 40C18-PREP (water:methanol) to give 6.12 mg of the title compound as a colorless flocculent material.

Workup

  1. customto remove insolubles
  2. washby washing twice with 5 ml of ethyl acetate and concentration under reduced pressure
  3. customThe concentrate is then freeze dried
  4. customto give a colorless flocculent material
  5. customThis material is then purified by column chromatography on Cosmosil 40C18-PREP (water:methanol)

Sources & evidence

ORD record
ord-c7fc6ff2f1e246d08dedcfa1b4ca7e39
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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