N-Methylaniline → (1R,5S,6S)-6-((1R)-1-Hydroxyethyl)-2-[(3S,5S)-5-[2(Z)-(imidazo[5,1-b]thiazol-3-yl)ethenyl]pyrrolidin-3-yl]thio-1-methylcarbapen-2-em-3-carboxylic acid

HRID 568248Notes

Reaction equation

HRID 568248 reaction equation
C(OC([N:7]1[C@H:11](/[CH:12]=[CH:13]\[C:14]2[N:15]3[CH:21]=[N:20][CH:19]=[C:16]3[S:17][CH:18]=2)[CH2:10][C@H:9]([S:22][C:23]2[C@H:24]([CH3:40])[C@@H:25]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:26]3[C:27]=2[C:28]([O:30]CC=C)=[O:29])[CH2:8]1)=O)C=C.CNC1C=CC=CC=1>ClCCl.CN(C=O)C.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:38][C@@H:36]([C@H:35]1[C:34](=[O:39])[N:26]2[C:27]([C:28]([OH:30])=[O:29])=[C:23]([S:22][C@H:9]3[CH2:10][C@@H:11](/[CH:12]=[CH:13]\[C:14]4[N:15]5[CH:21]=[N:20][CH:19]=[C:16]5[S:17][CH:18]=4)[NH:7][CH2:8]3)[C@H:24]([CH3:40])[C@H:25]12)[CH3:37]

Participants

6

Reactant 2

HCID 7515N-MethylanilineHCID 131722348HCID 131722348, compound

Product 1

HCID 131722347(1R,5S,6S)-6-((1R)-1-Hydroxyethyl)-2-[(3S,5S)-5-[2(Z)-(imidazo[5,1-b]thiazol-3-yl)ethenyl]pyrrolidin-3-yl]thio-1-methylcarbapen-2-em-3-carboxylic acidYield 18.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[2 (Z)-(imidazo[5,1-b]thiazol-3-yl)ethenyl]pyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate (80 mg) is dissolved in 1 ml of dichloromethane and 1 ml of DMF. N-Methylaniline (0.060 ml) and 40 mg of tetrakis(triphenylphosphine)palladium(0) are added thereto, and the mixture is stirred in an argon atmosphere at room temperature for 30 min. The reaction mixture is concentrated under reduced pressure. Ethyl acetate is added to the concentrate, and the resultant precipitate is collected by filtration and then purified by column chromatography on Cosmosil 40C18-PREP and Amberlyst A-26 (Cl− form) to give 11.9 mg of the title compound.

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. additionEthyl acetate is added to the concentrate
  3. filtrationthe resultant precipitate is collected by filtration
  4. custompurified by column chromatography on Cosmosil 40C18-PREP and Amberlyst A-26 (Cl− form)

Sources & evidence

ORD record
ord-dbf22796f5b34387a5b13a416a6ae4c6
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

Loading…