1-Bromo-3-chlorobenzene → Tert-butyl 3-(3-chlorophenyl)-3-oxopropyl(methyl)carbamate
Reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[CH:3]=1.CON(C)[C:12](=[O:24])[CH2:13][CH2:14][N:15]([CH3:23])[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19]>C1COCC1>[Cl:8][C:4]1[CH:3]=[C:2]([C:12](=[O:24])[CH2:13][CH2:14][N:15]([CH3:23])[C:16](=[O:22])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])[CH:7]=[CH:6][CH:5]=1Participants
Procedure
A solution of 1-bromo-3-chloro-benzene (57 g, 0.3 mmol) in dry THF (300 mL) was added drop wise to Mg (10.8 g, 0.45 mmol) at room temperature under N2. The mixture was stirred at refluxed for 1 h. The Grignard reagent was added drop wise to a solution of tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamate (37 g, 0.15 mmol) in dry THF (300 mL) at −78° C. After addition, the mixture was allowed to stir at room temperature overnight. The mixture was quenched with saturated NH4Cl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product, which was purified through column chromatography. 1H NMR (CDCl3, 400 MHz) δ 1.42 (s, 9H), 2.89 (s, 3H), 3.18 (m, 2H), 3.62 (t, 2H), 7.42 (m, 1H), 7.52 (m, 1H), 7.82 (m, 1H), 7.91 (m, 1H).
Workup
- temperatureat refluxed for 1 h
- additionAfter addition
- stirringto stir at room temperature overnight
- customThe mixture was quenched with saturated NH4Cl
- extractionextracted with ethyl acetate
- washThe combined organic layers were washed with brine
- dry with materialdried over Na2SO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-4f533c263aba482a980254f36437d87c
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08106221B2
Reaction notes
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