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

HRID 2220106Notes

Reaction equation

HRID 2220106 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) δ1.04 (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-3614992c4b5343229abb4ae43fa18c16
Source dataset
uspto-grants-2008_08
Patent number
US07417029B2

Reaction notes

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