p-Fluorophenethylamine → (s)-{[(4-Fluorobenzyl)methylcarbamoyl]phenylmethyl}carbamic acid tert-butyl ester

HRID 746994Notes

Reaction equation

HRID 746994 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]([C:16]([OH:18])=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])([CH3:4])[CH3:3].[F:19][C:20]1[CH:28]=[CH:27][C:23]([CH2:24][CH2:25][NH2:26])=[CH:22][CH:21]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:2]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:16](=[O:18])[NH:26][CH2:25][CH2:24][C:23]1[CH:27]=[CH:28][C:20]([F:19])=[CH:21][CH:22]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([CH3:1])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 4653p-FluorophenethylamineHCID 2733179PyBroPHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acid

Product 1

HCID 69267743(s)-{[(4-Fluorobenzyl)methylcarbamoyl]phenylmethyl}carbamic acid tert-butyl esterYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-Boc-L-phenylglycine (H, 17.2 g, 68.5 mmol) and (4-fluorobenzyl)methylamine (10.47 g, 75.3 mmol) in CH2Cl2 (550 mL) was cooled to 0° C. Disopropylethylamine (35.8 mL, 205 mmol) and PyBroP (38.3 g, 82.1 mmol) were then added sequentially. The cooling bath was removed and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the title compound (24.5 g, 96%) was isolated by chromatography on silica gel eluting with a gradient of 40% to 60% ethyl acetate in hexane. 1H NMR (selected signals, CDCl3): □6.02 (d, 0.3H), 5.56 (d, 0.7H), 2.83 (s, 0.9H), 2.78 (s, 2.1H), 1.40 (s, 6.3H, 1.39 (s, 2.7H).

Workup

  1. customThe cooling bath was removed
  2. customThe solvent was evaporated

Sources & evidence

ORD record
ord-b7407389642c43bd813dc7b9502d5e7b
Source dataset
uspto-grants-2008_07
Patent number
US07393958B2

Reaction notes

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