1,2-Dichloroethane → (S)-2-cyclopropylcarbamoyl-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1359746Notes

Reaction equation

HRID 1359746 reaction equation
[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([OH:15])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH:19]1([NH2:22])[CH2:21][CH2:20]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[CH2:4]([O:3][C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13](=[O:15])[NH:22][CH:19]1[CH2:21][CH2:20]1)=[O:2])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 101987Benzyloxycarbonyl-L-proline

Product 1

HCID 69997288(S)-2-cyclopropylcarbamoyl-pyrrolidine-1-carboxylic acid benzyl esterYield 85.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of carbobenzyloxy-L-proline (994 mg, 3.99 mmol), cyclopropylamine (0.41 mL, 5.9 mmol), HOBt (807 mg, 6 mmol), EDC (1.12 g, 5.9 mmol) and TEA (1.1 mL) in DMF (11 mL) was stirred at room temperature for 48 hours. The reaction was quenched with saturated sodium bicarbonate and extracted with dichloromethane. The organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was column chromatographed to give 985 mg (81%) of (S)-2-cyclopropylcarbamoyl-pyrrolidine-1-carboxylic acid benzyl ester.

Workup

  1. customThe reaction was quenched with saturated sodium bicarbonate
  2. extractionextracted with dichloromethane
  3. washThe organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customchromatographed

Sources & evidence

ORD record
ord-ff4ae6a4a34f441d9182894a06fff6d9
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

Loading…