2-(2-Benzyloxycarbonylamino-ethyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester → 2-(2-Benzyloxycarbonylamino-ethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1965154Notes

Reaction equation

HRID 1965154 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.CS(C)=O.O.C(OCC)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[O:13])[CH2:10][CH:9]1[CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 1

HCID 675057182-(2-Benzyloxycarbonylamino-ethyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 675061802-(2-Benzyloxycarbonylamino-ethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution containing 5 (10.2 g, 28.0 mmol) in DCM (100 mL) and DMSO (20 mL) was cooled to 0° C. TEA (14.1 g, 140 mmol) and SO3.pyridine complex (17.9 g, 112 mmol) were then added and the mixture stirred until homogeneous (approx. 45 min) then warmed to ambient temperature. After 3 h, the reaction mixture was diluted with water (200 mL) and diethyl ether (500 mL). The layers were separated and the organic phase was washed successively with 1N HCl, water, aqueous NaHCO3, water, and brine then dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (2:1 to 1:1 hexanes/EtOAc) to afford 9.34 g (92%) of 6 as a pale yellow-colored oil. 1H NMR (CDCl3, 300 MHz): δ7.32 (m, 5H), 5.90 (br s, 1H), 5.09 (app dd, J=19.4, 12.2 Hz, 2H), 4.52 (m, 1H), 3.95 (br d, 1H), 3.52 (m, 2H), 2.93 (m, 1H), 2.80 (dd, J=18.3, 9.3 Hz, 1H), 2.22 (br d, 1H), 1.69 (m, 1H), 1.55 (m, 1H), 1.57 (s, 9H) ppm. Mass spectrum, m/z [363.2] (M+H)+.

Workup

  1. additionpyridine complex (17.9 g, 112 mmol) were then added
  2. temperaturethen warmed to ambient temperature
  3. waitAfter 3 h
  4. customThe layers were separated
  5. washthe organic phase was washed successively with 1N HCl, water, aqueous NaHCO3, water, and brine
  6. dry with materialthen dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash silica gel chromatography (2:1 to 1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-7092ed1676b64cb0bf60ec26e721427d
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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