Ethyl 4-bromobutyrate → Ethyl 4-[(2,5-dimethoxyphenyl)ethylamino]butanoate
Reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][CH2:12][NH2:13].Br[CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].C(N(C(C)C)CC)(C)C>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][CH2:12][NH:13][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19]Participants
Procedure
(2,5-Dimethoxyphenyl)ethylamine 3 (8.33 gm, 0.046 moles), ethyl 4-bromobutyrate (11.64 gm, 0.060 moles) and diisopropylethylamine (7.76 gm, 0.060 moles) were stirred at 110-120° C. for 18 hours, cooled, and partitioned between 50 ml DCM and 50 ml water. The aqueous layer was extracted thrice with 50 ml portions of DCM. The combined organic extracts were washed with saturated NaCl, dried over Na2SO4, filtered, and concentrated by rotary evaporation under reduced pressure. The crude product was purified by flash chromatography on silica gel, eluting with a gradient mixture of ethyl acetate and hexane. Ethyl 4-[(2,5-dimethoxyphenyl)ethylamino]butanoate 4 (12.73 gm, 94% yield) was isolated after removing the solvent. 1H NMR (CDCl3) δ 6.44-6.78, 3H, m; 4.11, 2H, q; 3.79, 3H, s; 3.76, 3H, s; 3.08-3.19, 4H, m; 2.30, 2H, t; 1.79, 2H, m; 1.24, 3H, t; 1.03, 3H, t.
Workup
- temperaturecooled
- custompartitioned between 50 ml DCM and 50 ml water
- extractionThe aqueous layer was extracted thrice with 50 ml portions of DCM
- washThe combined organic extracts were washed with saturated NaCl
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated by rotary evaporation under reduced pressure
- customThe crude product was purified by flash chromatography on silica gel
- washeluting with a gradient mixture of ethyl acetate and hexane
Sources & evidence
- ORD record
- ord-b4ef648e398445ccaff645288501344c
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637658B2
Reaction notes
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