2-Fluoro-3-(trifluoromethyl)pyridine → (R)-4-(1-(3-(trifluoromethyl)pyridin-2-yloxy)ethyl)pyrimidin-2-amine
Reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C@H:8]([OH:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.CC([O-])(C)C.[K+].F[C:18]1[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:21]=[CH:20][N:19]=1>CN1CCOCC1>[F:25][C:24]([F:27])([F:26])[C:23]1[C:18]([O:10][C@@H:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)[CH3:9])=[N:19][CH:20]=[CH:21][CH:22]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
To a solution of (R)-1-(2-aminopyrimidin-4-yl)ethanol (6a) (250 mg) in dry N-methylmorpholine (4 mL) at ambient temperature was added potassium 2-methylpropan-2-olate (222 mg) and the solution was left to stir for 30 min then 2-fluoro-3-(trifluoromethyl)pyridine (282 mg) was added the mixture was stirred for 10 min at ambient temperature and then heated to 100° C. with microwave irradiation for 2 minutes then cooled and quenched into water (50 mL). The precipitated solid was filtered and washed with water and air dried under a slight vacuum. The semi-dried material was taken up in methylene chloride and dried over magnesium sulfate to which activated charcoal was added then filtered through a bed of dicalite and evaporated to give the title compound (359 mg), MS (ES): m/z 285 [M+H]+.
Workup
- waitthe solution was left
- stirringwas stirred for 10 min at ambient temperature
- temperaturethen cooled
- customquenched into water (50 mL)
- filtrationThe precipitated solid was filtered
- washwashed with water and air
- customdried under a slight vacuum
- dry with materialdried over magnesium sulfate to which activated charcoal
- additionwas added
- filtrationthen filtered through a bed of dicalite
- customevaporated
Sources & evidence
- ORD record
- ord-9f58f4fcee39497488336bafb3ce8db9
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952001B2
Reaction notes
Loading…