Phosphorus oxychloride → Ethyl 2-(tert-butyl)-4-chloropyrimidine-5-carboxylate

HRID 1098600Notes

Reaction equation

O=P(Cl)(Cl)[Cl:3].[C:6]([C:10]1[N:15]=[C:14](O)[C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][N:11]=1)([CH3:9])([CH3:8])[CH3:7]>C(N(CC)CC)C>[C:6]([C:10]1[N:15]=[C:14]([Cl:3])[C:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][N:11]=1)([CH3:9])([CH3:8])[CH3:7]

Participants

Conditions

Temperature: 40 °C

Procedure

In cold (˜0° C.) POCl3 (20 mL) was dropped triethylamine (0.55 mL) with stirring. To this was added in parts ethyl 2-tert-butyl-4-hydroxypyrimidine-5-carboxylate (2.18 g, 9.72 mmol). The mixture then warmed to 40° C. and stirred under Argon for 1 hour. The mixture was evaporated until free of POCl3, diluted with CHCl3 (100 mL) and poured carefully into ice (300 mL). The solution was stirred until it reached RT. The organic phase was separated, washed with sodium bicarbonate (100 mL), water (100 mL), dried (Na2SO4) and concentrated in vacuo to give ethyl 2-tert-butyl-4-chloropyrimidine-5-carboxylate (2.0 g, 85% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.12 (s, 1H), 4.34 (q, J=6.8 Hz, 2H), 1.33 (s, 9H), 1.27 (t, J=6.8 Hz, 3H); MS (ESI) m/z: 243.0 (M+H+).

Workup

stirringstirred under Argon for 1 hour
customThe mixture was evaporated until free of POCl3
additiondiluted with CHCl3 (100 mL)
additionpoured carefully into ice (300 mL)
stirringThe solution was stirred until it
customreached RT
customThe organic phase was separated
washwashed with sodium bicarbonate (100 mL), water (100 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-99a8d153dc214d399d18d320e70cb44a
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143293B2

Reaction notes

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