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

HRID 917206Notes

Reaction equation

HRID 917206 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-8f290b8f98ff4be8b53ad192c02c6c74
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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