Hydrochloric Acid → HCID 71008948, compound

Temperature

25 °C

A solution of (R)-2-methyl-propane-2-sulfinic acid {(R)-1-[1-(3-bromo-phenyl)-1H-pyrazol-4-yl]-2,2-difluoro-3-hydroxy-1-methyl-propyl}-amide (590 mg, 1.2 mmol) in methanol (5 ml) was treated at 0° C. with hydrochloric acid (4N in dioxane, 2.6 ml, 10.2 mmol), and the reaction mixture was stirred at 25° C. for 2 hours. For the workup, the solution was concentrated at reduced pressure, and the resultant residue was diluted with water (10 ml). The aqueous layer was treated with a saturated solution of sodium hydrogencarbonate to a pH of about 8, then extracted with ethyl acetate (4×10 ml). The combined organic layers were washed with brine (15 ml), dried over sodium sulphate, and evaporated at reduced pressure. The crude material thus obtained was purified by column chromatography on silica gel using a gradient of hexane/ethyl acetate=85:15 to 80:20 as the eluent to give the (R)-3-amino-3-[1-(3-bromo-phenyl)-1H-pyrazol-4-yl]-2,2-difluoro-butan-1-ol (400 mg, 96% yield) as a light yellow solid which was used in the next step without further purification. MS (ISP): m/z=346.5 [M+H]+.

1. concentrationFor the workup, the solution was concentrated at reduced pressure
2. additionthe resultant residue was diluted with water (10 ml)
3. additionThe aqueous layer was treated with a saturated solution of sodium hydrogencarbonate to a pH of about 8
4. extractionextracted with ethyl acetate (4×10 ml)
5. washThe combined organic layers were washed with brine (15 ml)
6. dry with materialdried over sodium sulphate
7. customevaporated at reduced pressure
8. customThe crude material thus obtained
9. customwas purified by column chromatography on silica gel using a gradient of hexane/ethyl acetate=85:15 to 80:20 as the eluent

ORD record

ord-1ac8f84decee4599a70d541a56f107b5

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785436B2