(R)-2-Methyl-CBS-oxazaborolidine → (3S)-4,4-Dimethoxytetrahydro-2H-pyran-3-ol

Temperature

40 °C

A 5-L 4-neck round bottom flask equipped with an overhead air stirrer, addition funnel with nitrogen inlet adapter, condenser, and a thermocouple was charged with (R)-(+)-2-methyl-CBS-oxazaborolidine (34 g, 0.12 mol) and THF (1.2 L). The mixture was warmed under nitrogen to 40° C. then Me2S—BH3 (63 mL, 0.67 mol) was added to the THF-catalyst mixture via syringe. An addition funnel was charged with 4,4-dimethoxydihydro-2H-pyran-3(4H)-one (as prepared in Intermediate 1, Step B, 96 g, 0.59 mol) in THF (1.2 L) was added drop wise over an 8 h period. After addition, the reaction was allowed to stir for 18 h at 40° C. The reaction was chilled to 10° C. in an ice-acetone bath and quenched by slow addition of MeOH (600 mL) over 45 min. The cooling bath was removed and the mixture allowed to warm to room temperature for 3 h. After the gas evolution ceased, the mixture was concentrated on a rotary evaporator to give 132 g. Purification on silica gel using a mixture of EtOAc and heptanes afforded the title compound (80.5 g, 83%, chiral GC 95% ee) as a yellow oil.

1. customA 5-L 4-neck round bottom flask equipped with an overhead air stirrer, addition funnel with nitrogen inlet adapter, condenser
2. additionwas added drop wise over an 8 h period
3. additionAfter addition
4. temperatureThe reaction was chilled to 10° C. in an ice-acetone bath
5. customquenched by slow addition of MeOH (600 mL) over 45 min
6. customThe cooling bath was removed
7. temperatureto warm to room temperature for 3 h
8. concentrationthe mixture was concentrated on a rotary evaporator
9. customto give 132 g
10. customPurification on silica gel using
11. additiona mixture of EtOAc and heptanes

ORD record

ord-7c4506f19227431bb8187cd9cc6ee84c

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150532B2