Reaction equation
[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:3]=1.[CH2:21]([Mg]Br)[CH3:22].CCCCCC.C(OCC)(=O)C>C1COCC1>[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](=[O:7])[CH2:21][CH3:22])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:3]=1Participants
Procedure
To a solution of 4-chloro-N-methoxy-N-methyl-2-phenylamino-benzamide (5.0 g, 17.2 mmol) in THF (60 mL) was added ethylmagnesium bromide (1M solution in THF, 70 mL, 70 mmol) dropwise at 0° C. under nitrogen. The mixture was slowly warmed to room temperature and stirred for 2 hr. Completion of the reaction was monitored by silica TLC (mobile phase; hexane:ethyl acetate=4:1; Rf=0.5). Reaction was quenched with an aqueous solution of 1N HCl (50 mL) at 0° C. and was extracted with ethyl acetate (2×300 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude material was purified using silica gel (100-200 mesh) column chromatography, using gradient polarity mobile phase (ethyl acetate:hexane=1:91:4), to give 1-(4-chloro-2-phenylamino-phenyl)-propan-1-one (4.15 g, 92.9% yield) as a yellow oil. 1H NMR (DMSO-d6) δ ppm 10.53 (s, 1H) 8.00 (d, J=8.7 Hz, 1H) 7.34-7.51 (m, 2H) 7.28 (d, J=7.7 Hz, 2H) 7.13-7.23 (m, 1H) 7.07 (d, J=1.8 Hz, 1H) 6.82 (dd, J=8.6, 1.9 Hz, 1H) 3.07 (q, J=7.2 Hz, 2H) 1.09 (t, J=7.3 Hz, 3H).
Workup
- customReaction
- customwas quenched with an aqueous solution of 1N HCl (50 mL) at 0° C.
- extractionwas extracted with ethyl acetate (2×300 mL)
- washThe combined organic layers were washed with water (100 mL), brine (100 mL)
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated under reduced pressure
- customThe crude material was purified
Sources & evidence
- ORD record
- ord-ecf48a573b4a4bb8b6155e59801df003
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08501732B2
Linked notes
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