N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide → 1-(2-Phenylamino-6-trifluoromethyl-pyridin-3-yl)-ethanone
Reaction equation
CON(C)[C:4](=[O:22])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[N:7][C:6]=1[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH3:24][Mg]Cl>O1CCCC1>[C:16]1([NH:15][C:6]2[C:5]([C:4](=[O:22])[CH3:24])=[CH:10][CH:9]=[C:8]([C:11]([F:12])([F:13])[F:14])[N:7]=2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
A solution of N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide (5.10 g, 15.7 mmol) in tetrahydrofuran (100 mL) cooled to 0° C. was treated with a solution of 3 M methylmagnesium chloride (15.7 mL, 47.0 mmol). The reaction was then stirred at 0° C. for 90 min. At this time, the reaction was warmed to 25° C. and was quenched with water (150 mL). The reaction was then partitioned between ethyl acetate (250 mL) and water (250 mL). The aqueous layer was back extracted with ethyl acetate (2×150 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (50 mL), filtered, rinsed with ethyl acetate and concentrated in vacuo. Flash chromatography (20%-40% ethyl acetate/hexanes) afforded 1-(2-phenylamino-6-trifluoromethyl-pyridin-3-yl)-ethanone (4.28 g, 97.4%) as a yellow solid.
Workup
- temperatureAt this time, the reaction was warmed to 25° C.
- customwas quenched with water (150 mL)
- customThe reaction was then partitioned between ethyl acetate (250 mL) and water (250 mL)
- extractionThe aqueous layer was back extracted with ethyl acetate (2×150 mL)
- washThe combined organics were washed with a saturated aqueous sodium chloride solution (50 mL)
- filtrationfiltered
- washrinsed with ethyl acetate
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-da45a705111c43e88e8a28c57aebe465
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08471027B2
Reaction notes
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