4,6-Dichloro-2-ethyl-5-fluoropyrimidine synthesis

Yield:1152109-89-1 85%

Reaction Conditions:

with trichlorophosphate at 125; for 4 h;

Steps:

D.B

Part B: 4,6-Dichloro-2 -ethyl -5-fluoropyrimidine. 2-Ethyl-5-fluoro-6-hydroxy-4(1H)-pyrimidinone (20 g, 126.6 mmol) in POCI₃ (58 ml_, 633 mmol) was heated at 125 ⁰C (oil bath) for 2 h. An additional 68 ml. of fresh POCI₃ was added to the hot solution. The resulting solution was heated for an additional 2 h until all the starting material was consumed. The excess POCI₃ was distilled (62 ⁰C - 68 ⁰C) in vacuo to give a light brown residue. After being cooled to room temperature, the residue was diluted with 50 ml. of CH₂Cb, then poured into ice water (200 ml_). To this mixture was added 200 ml. of CH₂CI₂ and the subsequent mixture was stirred for 10 min. After separation of the two layers, the aqueous layer was further extracted with 100 ml. ofCH₂CI₂. The combined organic layers were dried over Na₂SO₄, then filtered through a short silica gel pad, which was then washed with 150 ml. of 1% MeOH in CH₂CI₂.Evaporation of the solvent provided 4,6-dichloro-2-ethyl-5-fluoropyrimidine (21 g, 85%) as a light yellow liquid. LCMS: (M+H)⁺: not detected.

References:

WO2009/61879,2009,A1 Location in patent:Page/Page column 62