Tetrahydrofuran → (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide

Temperature

-10 °C

To a 100-mL round-bottomed flask were added a mixture of (R)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate and (5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate (0.33 g, 0.697 mmol) and DCM (6.97 ml). The solution was cooled to −10° C. and lithium aluminum hydride, 1.0m solution in THF (1.394 ml, 1.394 mmol) was added dropwise over 10 min. The reaction mixture was stirred −10° C. for 4 h. Sodium sulfate decahydrate (1.8 g, 5.6 mmol) was added and the mixture was stirred for 10 min. The solid was filtered and washed with EtOAc. The filtrate was concentrated in vacuo. Purification by silica gel chromatography (0-70% EtOAc/hexane) afforded a 3:1 mixture of (R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide and (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide (0.176 g, 0.436 mmol, 62.6% yield) as a colorless oil. MS m/z=403, 405 M+ Calculated for C13H18BrF3N2O2S: 403.26. Used directly in the following step.

1. additionTo a 100-mL round-bottomed flask were added
2. stirringthe mixture was stirred for 10 min
3. filtrationThe solid was filtered
4. washwashed with EtOAc
5. concentrationThe filtrate was concentrated in vacuo
6. customPurification by silica gel chromatography (0-70% EtOAc/hexane)
7. customafforded

ORD record

ord-e5e28ddf851a48fb944c4a74e2a3b83d

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2