Potassium Carbonate → 6,6-difluoro-2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

HRID 570127

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([OH:13])[NH:10][N:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].CS(O[CH2:25][C:26]([F:34])([F:33])[CH2:27]OS(C)(=O)=O)(=O)=O>CN(C=O)C.O>[F:33][C:26]1([F:34])[CH2:27][O:13][C:11]2=[CH:12][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[N:9][N:10]2[CH2:25]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 3-(4-fluorophenyl)-1H-pyrazol-5-ol (4 g, 22.47 mmol) in DMF (30 mL) was added K2CO3 (12.4 g, 89.88 mmol) and 2,2-difluoropropane-1,3-diyl dimethanesulfonate (9 g, 33.7 mmol) at room temperature and then stirred for 16 h at 60° C. The progress of the reaction was monitored by TLC. Thereafter, the reaction mixture was diluted with cold water and extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulphate and concentrated to get the crude product. Purification by column chromatography over silica gel (eluent 5-10% ethyl acetate in petrol ether) yielded 6,6-difluoro-2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (3.2 g, 56%) as an off-white solid.

Workup

extractionextracted with diethyl ether
dry with materialThe organic layer was dried over anhydrous sodium sulphate
concentrationconcentrated
customto get the crude product
customPurification by column chromatography over silica gel (eluent 5-10% ethyl acetate in petrol ether)

Sources & evidence

ORD record: ord-ca030abcf55f4cd2950e44fc900b0eee
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023844B2

Linked notes

Loading…