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

HRID 599316Notes

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 of 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 at RT to melt. The organic phase was separated, washed with sodium bicarbonate (100 mL), water (100 mL) and dried (Na2SO4). The solvents evaporated 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 at RT
customThe organic phase was separated
washwashed with sodium bicarbonate (100 mL), water (100 mL)
dry with materialdried (Na2SO4)
customThe solvents evaporated

Sources & evidence

ORD record: ord-e2afc02351b7441d953cf48152b7a88b
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897762B2

Reaction notes

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