Phenol → 4,5-Difluoro-6-phenoxypyrimidine

HRID 2304818Notes

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-2931ca2e58f74826aaec9d0a3d3421a3
Source dataset: uspto-grants-2002_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06437127B1

Reaction notes

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