Sodium Bicarbonate → Tert-butyl 2-[(3-cyano-5-fluorobenzyl)amino]-4-methylpentanoate

HRID 572550Notes

Reaction equation

HRID 572550 reaction equation
BrCC1[CH:4]=[C:5]([CH:8]=[C:9]([F:11])[CH:10]=1)[C:6]#[N:7].C(=O)(O)[O-].[Na+].Cl.[C:18]([O:22][C:23](=[O:32])[C@@H:24]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH:25][CH2:26][CH3:27])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C.O>[C:6]([C:5]1[CH:4]=[C:27]([CH:10]=[C:9]([F:11])[CH:8]=1)[CH2:26][NH:25][CH:24]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:23]([O:22][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:32])#[N:7]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 666526293-(Bromomethyl)-5-fluorobenzonitrileHCID 86683829ethyl D-leucine tert-butyl ester hydrochloride

Product 1

HCID 66653018Tert-butyl 2-[(3-cyano-5-fluorobenzyl)amino]-4-methylpentanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To 3-(bromomethyl)-5-fluorobenzonitrile (4.0 g, 0.02 mol) in dry DMF (40 mL) were added sodium bicarbonate (3.9 g, 0.046 mol) and ethyl D-leucine tert-butyl ester hydrochloride (4.2 g, 0.019 mol). The reaction mixture was stirred at RT for 16 hours. It was diluted with water and extracted with ethyl acetate. The organic phase was washed with water, brine, dried and concentrated. The crude product was purified by chromatography using petroleum ether/ethyl acetate as eluent, affording the title compound as a colorless liquid. 1H NMR (DMSO-d6, 400 MHz): δ 7.68 (d, J=9.5 Hz, 1H), 7.63 (s, 1H), 7.53 (d, J=9.8 Hz, 1H), 3.78 (d, 1H), 3.64 (d, 1H), 2.97 (d, 1H), 2.60 (brs, 1H), 1.97-1.71 (m, 1H), 1.36 (m, 11H), 0.86 (d, 3H), 0.80 (d, 3H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with water, brine
  3. customdried
  4. concentrationconcentrated
  5. customThe crude product was purified by chromatography

Sources & evidence

ORD record
ord-bcce3e61c9314fc5b18183fc1762c4e5
Source dataset
uspto-grants-2015_05
Patent number
US09029405B2

Reaction notes

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