Benzyl chloroformate → Benzyl 4-hydroxy-3,3-dimethylpyrrolidine-1-carboxylate

HRID 877704Notes

Reaction equation

HRID 877704 reaction equation
[CH3:1][C:2]1([CH3:8])[CH2:6][NH:5][CH2:4][CH:3]1[OH:7].[OH-].[Na+].[C:11](Cl)(=[O:20])[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>ClCCl.O>[OH:7][CH:3]1[CH2:4][N:5]([C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:20])[CH2:6][C:2]1([CH3:8])[CH3:1]

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 553001584,4-Dimethylpyrrolidin-3-ol

Product 1

HCID 68291226Benzyl 4-hydroxy-3,3-dimethylpyrrolidine-1-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4,4-dimethylpyrrolidin-3-ol (2.58 g, 22.4 mmol) in dichloromethane (90 mL), was added 1N sodium hydroxide (90 mL, 90 mmol), then benzyl carbonochloridate (4.16 mL, 24.6 mmol) at rt. The mixture was vigorously stirred for 18 h. The reaction was diluted with dichloromethane and water. The organic phase was separated, dried and concentrated. The crude was purified by silica gel chromatography, eluting with 20-50% ethyl acetate in hexanes to afford benzyl 4-hydroxy-3,3-dimethylpyrrolidine-1-carboxylate (4.07 g, 73% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.52-7.28 (m, 5H), 5.14 (s, 2H), 3.97-3.80 (m, 1H), 3.74 (td, J=11.3, 5.2 Hz, 1H), 3.49 (d, J=5.5 Hz, 1H), 3.43-3.18 (m, 2H), 1.74 (br. s., 1H), 1.09 (d, J=3.3 Hz, 3H), 1.03 (d, J=4.6 Hz, 3H). MS (ES+) m/z: 250.1 (M+H); LC retention time: 2.84 min (analytical HPLC Method I).

Workup

  1. customat rt
  2. customThe organic phase was separated
  3. customdried
  4. concentrationconcentrated
  5. customThe crude was purified by silica gel chromatography
  6. washeluting with 20-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0987dfe8ad8849518064a90a20aae2c4
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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