Reaction #657309

Reaction equation

3-(4-fluorophenyl)-1H-pyrazol-5-ol

K2CO3

2,2-difluoropropane-1,3-diyl dimethanesulfonate

→

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

Yield 56.0%

Solvents

DMF

water

Conditions

Workup

1. 1
   Extractionextracted with diethyl ether
2. 2
   DryingThe organic layer was dried over anhydrous sodium sulphate
3. 3
   Concentrationconcentrated
4. 4
   Otherto get the crude product
5. 5
   OtherPurification by column chromatography over silica gel (eluent 5-10% ethyl acetate in petrol ether)

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.

Source