Borane → Benzyl 4-amino-3,3-dimethylpyrrolidine-1-carboxylate

HRID 877707Notes

Reaction equation

HRID 877707 reaction equation
CO/[N:3]=[C:4]1/[C:5]([CH3:20])([CH3:19])[CH2:6][N:7]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8]/1.B>O1CCCC1>[NH2:3][CH:4]1[CH2:8][N:7]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:6][C:5]1([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 6331BoraneHCID 87210112benzyl (4Z)-4-methoxyimino-3,3-dimethylpyrrolidine-1-carboxylate

Product 1

HCID 66936024Benzyl 4-amino-3,3-dimethylpyrrolidine-1-carboxylateYield 67.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (Z)-benzyl 4-(methoxyimino)-3,3-dimethylpyrrolidine-1-carboxylate (3.17 g, 11.5 mmol) in tetrahydrofuran (10 mL), was added borane in THF (24.1 mL, 24.1 mmol) at rt. The reaction was heated at reflux overnight. The reaction was cooled, quenched with 6N aq. sodium hydroxide, then diluted by water, and extracted with ether. The organic layer was dried over MgSO4, concentrated, and purified by silica gel chromatography, eluting with 0-20% methanol in dichloromethane to give benzyl 4-amino-3,3-dimethylpyrrolidine-1-carboxylate (1.92 g, 67.4 yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.45-7.31 (m, 5H), 5.32 (s, 2H), 5.15 (s, 2H), 4.07-3.91 (m, 1H), 3.56 (dd, J=12.1, 6.4 Hz, 1H), 3.51-3.32 (m, 1H), 3.22-3.06 (m, 1H), 2.83-2.75 (m, 1H), 1.17 (s, 3H), 1.10 (s, 3H). MS (ES+) m/z: 248.2, 249.1 (M+H); LC retention time: 2.24 min (analytical HPLC Method I).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux overnight
  3. temperatureThe reaction was cooled
  4. customquenched with 6N aq. sodium hydroxide
  5. additiondiluted by water
  6. extractionextracted with ether
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography
  10. washeluting with 0-20% methanol in dichloromethane

Sources & evidence

ORD record
ord-8108d76483164400843fb7e0876c4a18
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…