Phosphorus oxychloride → Ethyl 4-chloro-2-methylpyrimidine-5-carboxylate
Reaction equation
P(Cl)(Cl)([Cl:3])=O.O[C:7]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:10]=[C:9]([CH3:18])[N:8]=1>C(N(CC)CC)C>[Cl:3][C:7]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:10]=[C:9]([CH3:18])[N:8]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 40 °C
Procedure
In cold (˜0° C.) phosphorous oxychloride (40 mL) was carefully added triethylamine (1.87 mL) with stirring. To this was added, in parts, ethyl 4-hydroxy-2-methylpyrimidine-5-carboxylate (5.00 g, 27.4 mmol). The mixture then warmed to 40° C. and stirred under Argon for 2 hours. The mixture was evaporated free of phosphorous oxychloride, diluted with chloroform (150 mL) and poured carefully into ice (400 mL) and allowed to warm to RT. The organic phase was separated, washed with saturated sodium bicarbonate (75 mL), then brine (100 mL) and dried over sodium sulfate. The solvents evaporated to give a thick oil which was purified by chromatography (Biotage Si-40 column, 15-40% ethyl acetate/hexane) to give ethyl 4-chloro-2-methylpyrimidine-5-carboxylate as a clear oil (2.96 g, 53% yield). 1H NMR (400 MHz, DMSO-d6): δ 1.31 (t, 3 H), 2.66 (s, 3 H), 4.34 (q, 2 H), 9.06 (s, 1 H); MS (ESI) m/z: 201.0 (M+H+).
Workup
- stirringstirred under Argon for 2 hours
- customThe mixture was evaporated free of phosphorous oxychloride
- additiondiluted with chloroform (150 mL)
- additionpoured carefully into ice (400 mL)
- temperatureto warm to RT
- customThe organic phase was separated
- washwashed with saturated sodium bicarbonate (75 mL)
- dry with materialbrine (100 mL) and dried over sodium sulfate
- customThe solvents evaporated
- customto give a thick oil which
- customwas purified by chromatography (Biotage Si-40 column, 15-40% ethyl acetate/hexane)
Sources & evidence
- ORD record
- ord-2b2f35e8fb4846e9a8ad201e00d0f4d2
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188113B2
Reaction notes
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