Acetic Acid → 1-Pyrrolidinecarboxylic acid, 3-[(1-methylethyl)amino]-, 1,1-dimethylethyl ester

HRID 242670Notes

Reaction equation

HRID 242670 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[CH3:14][C:15]([CH3:17])=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[C:10]([O:9][C:7]([N:4]1[CH2:5][CH2:6][CH:2]([NH:1][CH:15]([CH3:17])[CH3:14])[CH2:3]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 533466421-Pyrrolidinecarboxylic acid, 3-[(1-methylethyl)amino]-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (R)-3-amino-1-N-Boc pyrrolidine (1.0 eq, 2.68 mmol) in methanol (15 mL) was added acetone (1.07 eq), sodium cyano borohydride (2.0 eq) and few drops of acetic acid and the resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The combined organics were washed with brine and dried over sodium sulfate. The crude product was purified on silica using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (30%). 1H-NMR (CDCl3) δ: 1.05 (6H, d), 1.45 (9H, s), 1.60 (1H, m), 2.80-3.00 (2H, m), 3.20-3.70 (4H, m). ESI-MS m/z: 229 (M+1), UV retention time: 0.77 min.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in dichloromethane
  3. washwashed with saturated aqueous sodium bicarbonate
  4. washThe combined organics were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customThe crude product was purified on silica using gradient elution from hexane/ethyl acetate (5%) to hexane/ethyl acetate (30%)

Sources & evidence

ORD record
ord-9c056779ec05416398d66c313a94a6a4
Source dataset
uspto-grants-2014_02
Patent number
US08653096B2

Reaction notes

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