Phenol → 4,5-Difluoro-6-phenoxypyrimidine

HRID 1857966Notes

Reaction equation

CC(C)([O-])C.[K+].[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C1([O-])C=CC=CC=1.[K+].[F:22][C:23]1[C:28]([F:29])=[C:27](F)[N:26]=[CH:25][N:24]=1>C1COCC1>[F:29][C:28]1[C:27]([O:13][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:26][CH:25]=[N:24][C:23]=1[F:22]

Participants

Conditions

Temperature: 0 °C

Procedure

With stirring, 50.4 g (0.45 mol) of potassium tert-butoxide (M=112.22) are added to a solution of 42.4 g (0.45 mol) of phenol in 400 ml of THF. The resulting potassium phenolate solution is added dropwise to a solution of 80 g (0.6 mol) of 4,5,6-trifluoropyrimidine in 1 l of THF which had been cooled to 0° C., and the mixture is stirred for 30 minutes. The solution is concentrated under reduced pressure and the residue is mixed with water and extracted with ethyl acetate. The organic phase is separated off, dried over sodium sulphate and concentrated under reduced pressure. The crude product is stirred with petroleum ether and filtered off. 63.8 g (68.1% of theory) of 5,6-difluoro-4-phenoxypyrimidine of melting point 65-66° C. are obtained.

Workup

stirringthe mixture is stirred for 30 minutes
concentrationThe solution is concentrated under reduced pressure
additionthe residue is mixed with water
extractionextracted with ethyl acetate
customThe organic phase is separated off
dry with materialdried over sodium sulphate
concentrationconcentrated under reduced pressure
stirringThe crude product is stirred with petroleum ether
filtrationfiltered off

Sources & evidence

ORD record: ord-c9ac4c0cdb5144079daf4b6d32e6173c
Source dataset: uspto-grants-2000_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06150374

Reaction notes

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