1,2-Dichloroethane → 1-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 910012Notes

Reaction equation

HRID 910012 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[C:34]([O:38][C:39](=[O:45])[C@@H:40]1[CH2:44][CH2:43][CH2:42][NH:41]1)([CH3:37])([CH3:36])[CH3:35]>C(Cl)Cl.CN(C)C=O>[C:34]([O:38][C:39]([CH:40]1[CH2:44][CH2:43][CH2:42][N:41]1[C:13](=[O:15])[CH:12]([NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:45])([CH3:37])([CH3:35])[CH3:36]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 34012063,3-dimethyl-2-(phenylmethoxycarbonylamino)butanoic acidHCID 6453108L-Proline 1,1-dimethylethyl ester

Product 1

HCID 666982781-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-pyrrolidine-2-carboxylic acid tert-butyl esterYield 991.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2 (6.01 g, 2.0 mmol) in CH2Cl2 (30 ml) and anhydrous DMF (dimethylformamide)(10 ml) at 0° C. was added HOBT (3.16 g, 2.0 mmol), EDC (1-(3-dimethylaminopropyl-3-ethyl-carbodiimide hydrochloride) (7.19 g, 4.0 mmol) and L-proline-tert-butyl ester (4.22 g, 2.0 mmol). The solution was stirred at 0° C. for 10 minutes, then at room temperature for 5 hours. The solvents were evaporated in-vacuo and the resulting oil dissolved in EtOAc which was washed with H2O (3×200 ml) and brine (200 ml). The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to give the crude product. Flash chromatography on silica gel using hexanes/EtOAc (95/5 to 80/20%) afforded the title compound as a colorless oil (8.30 g, 87.5% yield): 1H-NMR (500 MHz, CDCl3) □ 1.04 (s, 9H), 1.45 (s, 9H), 1.89-1.96 (m, 2H), 2.02-2.05 (m, 1H), 2.18-2.22 (m, 1H), 3.65-3.69 (m, 1H), 3.79-3.82 (m, 1H), 4.34-4.37 (m, 2H), 5.03-5.19 (m, 2H), 5.53 (d, 1H), 7.26-7.38 (5H).

Workup

  1. waitat room temperature for 5 hours
  2. customThe solvents were evaporated in-vacuo
  3. dissolutionthe resulting oil dissolved in EtOAc which
  4. washwas washed with H2O (3×200 ml) and brine (200 ml)
  5. dry with materialThe organic phase was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude product

Sources & evidence

ORD record
ord-f9722c15cdfb4ce69866c46545124588
Source dataset
uspto-grants-2011_09
Patent number
US08022041B2

Reaction notes

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