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

HRID 917209Notes

Reaction equation

HRID 917209 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-121ba5bfff8742a4b305a8020a408fce
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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