Chloroacetyl chloride → N-[(R)-1-(3-Bromo-5-nitro-phenyl)-2-hydroxy-1-methyl-ethyl]-2-chloro-acetamide

HRID 2196245Notes

Reaction equation

[NH2:1][C@@:2]([C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[C:8]([Br:15])[CH:7]=1)([CH3:5])[CH2:3][OH:4].C([O-])([O-])=O.[K+].[K+].CCN(C(C)C)C(C)C.[Cl:31][CH2:32][C:33](Cl)=[O:34]>CN(C=O)C.C1(C)C=CC=CC=1.O>[Br:15][C:8]1[CH:7]=[C:6]([C@:2]([NH:1][C:33](=[O:34])[CH2:32][Cl:31])([CH3:5])[CH2:3][OH:4])[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(R)-2-Amino-2-(3-bromo-5-nitro-phenyl)-propan-1-ol (6.27 g, 22.79 mmol) was dissolved in DMF (230 ml) under N2 and K2CO3 (7.87 g, 57 mmol) and DIPEA (3.98 ml, 22.79 mmol) were added. The mixture was cooled to 0° C. and chloro-acetylchloride (2.83 g, 25.07 mmol) was added dropwise. The reaction was stirred at 0° C. for 19 hrs. After completion, the reaction was put between water (2.3 liter) and toluene (2.3 l). The organic phases were washed with water and brine, combined and dried over Na2SO4. Volatiles were removed under reduced pressure. The crude product was purified by automated column chromatography (cyclohexane/ethyl acetate) yielding the title compound as colorless oil. 1H-NMR (360 MHz, DMSO-d6): 8.51 (1H, NH), 8.28 (s, 1H), 8.12 (s, 1H), 7.93 (s, 1H), 5.25 (t, 1H), 4.15 (d, 2H), 3.62 (m, 2H), 1.62 (s, 3H); MS: 351 [(M+H)+].

Workup

washThe organic phases were washed with water and brine
dry with materialdried over Na2SO4
customVolatiles were removed under reduced pressure
customThe crude product was purified by automated column chromatography (cyclohexane/ethyl acetate)

Sources & evidence

ORD record: ord-fc0091fc276e4c2d8e993dd5e02d7b5e
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08338413B1

Reaction notes

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