tert-butyl 3,5-difluoro-4-(hydroxymethyl)benzoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of tert-butyl 3,5-difluoro-4-(hydroxymethyl)benzoate (1.9 g, 7.78 mmol) in DCM was added Et3N (3.27 mL, 23.4 mmol, 3 eq) and methanesulfonylchloride (0.72 mL, 9.3 mmol, 1.2 eq) successively at 0° C. After the reaction was stirred for 30 min, it was extracted with CH2Cl2C and water. Organic layer was dried over MgSO4 and evaporated in vacuo. The residue was purified by column chromatography (Hex/EtOAc=4:1) to give tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoate (2.25 g, 89% yield) as a ivory solid. it was extracted with CH2Cl2C and water Organic layer was dried over MgSO4 evaporated in vacuo The residue was purified by column chromatography (Hex/EtOAc=4:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of tert-butyl 3,5-difluoro-4-formylbenzoate (21 g, 86.7 mmol) in MeOH was portionwise added NaBH4 (3.28 g, 86.7 mmol) at 0° C. After 20 min, the reaction mixture was evaporated in vacuo and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography (Hex/EtOAc=4:1) to give tert-butyl 3,5-difluoro-4-(hydroxymethyl)benzoate (20.7 g, 97%) as a white solid. at 0° C the reaction mixture was evaporated in vacuo the product was extracted with ethyl acetate The organic layer was washed with brine dried over MgSO4 evaporated in vacuo The residue was purified by flash column chromatography (Hex/EtOAc=4:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of tert-butyl 3,5-difluoro-4-(hydroxymethyl)benzoate (1.9 g, 7.78 mmol) in DCM was added Et3N (3.27 mL, 23.4 mmol, 3 eq) and methanesulfonylchloride (0.72 mL, 9.3 mmol, 1.2 eq) successively at 0° C. After the reaction was stirred for 30 min, it was extracted with CH2Cl2C and water. Organic layer was dried over MgSO4 and evaporated in vacuo. The residue was purified by column chromatography (Hex/EtOAc=4:1) to give tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoate (2.25 g, 89% yield) as a ivory solid. it was extracted with CH2Cl2C and water Organic layer was dried over MgSO4 evaporated in vacuo The residue was purified by column chromatography (Hex/EtOAc=4:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of tert-butyl 3,5-difluoro-4-formylbenzoate (21 g, 86.7 mmol) in MeOH was portionwise added NaBH4 (3.28 g, 86.7 mmol) at 0° C. After 20 min, the reaction mixture was evaporated in vacuo and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography (Hex/EtOAc=4:1) to give tert-butyl 3,5-difluoro-4-(hydroxymethyl)benzoate (20.7 g, 97%) as a white solid. at 0° C the reaction mixture was evaporated in vacuo the product was extracted with ethyl acetate The organic layer was washed with brine dried over MgSO4 evaporated in vacuo The residue was purified by flash column chromatography (Hex/EtOAc=4:1)