Phosphorus oxychloride → (2S)-7-chloro-2-methyl-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Reaction equation
O[C:2]1[N:3]=[C:4]2[NH:11][C@:10]([CH3:16])([C:12]([F:15])([F:14])[F:13])[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.P(Cl)(Cl)([Cl:19])=O>ClCCCl>[Cl:19][C:2]1[N:3]=[C:4]2[NH:11][C@:10]([CH3:16])([C:12]([F:15])([F:14])[F:13])[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 70 °C
Procedure
To a suspension of 5.6 g of (2S)-7-hydroxy-2-methyl-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one in 100 mL of 1,2-dichloroethane, are added at room temperature and under an argon atmosphere, 11 mL of phosphorus oxychloride. The resulting mixture is then heated to 70° C. After two hours of stirring and after monitoring with LC/MS, the reaction is completed. After cooling, the reaction mixture is dry evaporated under reduced pressure. The obtained residue is taken up with 5 mL of cold water and 200 mL of ethyl acetate. On the obtained mixture, 32% soda is added up to a pH=6. The organic phase is then separated and then dried on magnesium sulphate, filtered and concentrated under reduced pressure in order to obtain 6 g of (2S)-7-chloro-2-methyl-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one including the following characteristics:
Workup
- additionare added at room temperature and under an argon atmosphere
- temperatureAfter cooling
- customthe reaction mixture is dry
- customevaporated under reduced pressure
- additionOn the obtained mixture, 32% soda is added up to a pH=6
- customThe organic phase is then separated
- customdried on magnesium sulphate
- filtrationfiltered
- concentrationconcentrated under reduced pressure in order
Sources & evidence
- ORD record
- ord-ffd53f30bb3e490192ce05f598935534
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08815853B2
Reaction notes
Loading…