Thionyl Chloride → 2-(chloromethyl)-3-hydroxy-6-methyl-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one hydrochloride
Reaction equation
[OH:1][C:2]1[C:7](=[O:8])[CH:6]=[C:5]([CH3:9])[N:4]([CH2:10][C:11]([F:14])([F:13])[F:12])[C:3]=1[CH2:15]O.S(Cl)([Cl:19])=O>C(#N)C>[ClH:19].[Cl:19][CH2:15][C:3]1[N:4]([CH2:10][C:11]([F:14])([F:13])[F:12])[C:5]([CH3:9])=[CH:6][C:7](=[O:8])[C:2]=1[OH:1]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
3-Hydroxy-2-(hydroxymethyl)-6-methyl-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one (375 mg, 1.6 mmol) was mixed with acetonitrile at 80° C. and the thionyl chloride (753 mg, 6.3 mmol) was added. The reaction mixture was stirred for 5 minutes and then concentrated by rotary evaporator to give 2-(chloromethyl)-3-hydroxy-6-methyl-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one hydrochloride. The chloride compound was added to a solution of piperidine (672 mg, 7.9 mmol) in isopropanol (5 mL) at room temperature. Five minutes later, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water twice and brine, dried and concentrated. The residue was triturated with ether/hexanes to give 3-hydroxy-6-methyl-2-(piperidin-1-ylmethyl)-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one (165 mg) as pale orange solid. Yield=34%; 1H NMR (MeOD-D4, 90 MHz) δ (ppm): 6.37 (s, 1H), 3.72 (br. s, 2H), 2.45 (br. m, 7H) and 1.51 (br. m, 6H); MS m/z 305 [M+1]+.
Workup
- concentrationconcentrated by rotary evaporator
Sources & evidence
- ORD record
- ord-03b4240580b041d4a20f89fe66e446c8
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073865B2
Reaction notes
Loading…