Acetic Acid → 3-[(4-Chloro-benzyl)-isobutyl-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 242667Notes

Reaction equation

HRID 242667 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:22](=O)[CH:23]([CH3:25])[CH3:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6561IsobutyraldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 667576703-(4-Chloro-benzylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 667581663-[(4-Chloro-benzyl)-isobutyl-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 3-(4-chloro-benzylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.4 g, 1.28 mmol) and isobutyraldehyde (0.14 g, 1.92 mmol) in dichloroethane was added sodium triacetoxy borohydride (0.81 g, 3.85 mmol) and catalytic acetic acid. The resulting reaction 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 (10%) to hexane/ethyl acetate (50%). 1H-NMR (CDCl3) δ: 0.80 (6H, 2×d), 1.45 (9H, s), 1.60-1.90 (2H, m), 2.20 (2H, d), 3.00-3.70 (7H, m), 7.20 (4H, s). ESI-MS m/z: 367 (M+1), UV retention time: 1.89 min.

Workup

  1. customThe resulting reaction mixture
  2. concentrationThe reaction mixture was concentrated
  3. dissolutiondissolved in dichloromethane
  4. washwashed with saturated aqueous sodium bicarbonate
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe crude product was purified on silica using gradient elution from hexane/ethyl acetate (10%) to hexane/ethyl acetate (50%)

Sources & evidence

ORD record
ord-0391aa76a7584854935faef31d237267
Source dataset
uspto-grants-2014_02
Patent number
US08653096B2

Reaction notes

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