Phosphorus oxychloride → 6-Chloro-5-(trifluoromethyl)pyrimidin-4-amine
Reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4](O)[C:3]=1[C:9]([F:12])([F:11])[F:10].O=P(Cl)(Cl)[Cl:15]>>[Cl:15][C:4]1[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=1[C:9]([F:12])([F:11])[F:10]Participants
3
Conditions
- Temperature
- 100 °C
Procedure
The mixture of 6-amino-5-(trifluoromethyl)pyrimidin-4-ol (N-4) (300 mg, 1.66 mmol) in POCl3 (8 mL) in a pressure vessel is stirred at 100° C. for 1 h. The mixture is allowed to cool to RT and concentrated in vacuo. The residue is taken up in water (20 mL), basified with saturated NaHCO3 aqueous solution to pH=9 and then extracted with DCM (30 mL×3). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo to afford the desired product, 6-chloro-5-(trifluoromethyl)pyrimidin-4-amine (N-5) as a yellow solid.
Workup
- temperatureto cool to RT
- concentrationconcentrated in vacuo
- extractionextracted with DCM (30 mL×3)
- washThe combined organic layers are washed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationThe filtrate is concentrated in vacuo
Sources & evidence
- ORD record
- ord-15dca0a8596f451e82ecc913e4affb8f
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181221B2
Reaction notes
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