(Dimethyl sulfide)trihydroboron → 5,7-Difluorochroman-4-ol

To a mixture of 1 M (S)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole toluene solution (5.43 mL, 5.43 mmol) and tetrahydrofuran (40 mL) was added 2M borane-methyl sulfide complex tetrahydrofuran solution (29.8 mL, 59.7 mmol) at 0° C. and the mixture was stirred for 20 minutes. To the mixture was added a solution of 5,7-difluoro-2,3-dihydro-4H-chromen-4-one (10.0 g, 54.3 mmol, STEP 7) in tetrahydrofuran (70 mL) at 0° C. over a period of 1 hour, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was quenched with methanol (50 mL) and stirred for 30 minutes at room temperature. The mixture was concentrated in vacuum and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1 as an eluent) to afford crude white solids (8.85 g, 86% ee). The solids were recrystallized from hexane (300 mL) to give the title compound as a colorless needle crystal (5.90 g, 58%, >99% ee).

1. stirringthe mixture was stirred at the same temperature for 1 hour
2. customThe reaction mixture was quenched with methanol (50 mL)
3. stirringstirred for 30 minutes at room temperature
4. concentrationThe mixture was concentrated in vacuum
5. customthe residue was purified by column chromatography on silica gel (hexane
6. customethyl acetate=4:1 as an eluent) to afford crude white solids (8.85 g, 86% ee)
7. customThe solids were recrystallized from hexane (300 mL)

ORD record

ord-9c174087e2874cad820763f0af66a04c

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723321B2