Sodium Bicarbonate → HCID 59235369, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-bromo-1-chloro-2-(4-cyclopropylbenzyl)benzene (6.6 g, 20.5 mmol) in dry THF/toluene (90 mL, 1:2) at −78° C. under argon was added dropwise n-BuLi (9.84 mL, 24.62 mmol, 2.5 N in hexane) over 10 minutes, and then the mixture was stirred for 30 minutes at −70° C. A solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (12.4 g, 26.6 mmol) in anhydrous toluene (30 mL) was added dropwise over 5 minutes, and the reaction solution was stirred for 1 hour at −65° C. The reaction was quenched by addition of saturated aq. ammonium chloride (100 mL) at 0° C., the organic layer was separated, and the aqueous layer was extracted with toluene (30 mL). The combined organic phases were concentrated under reduced pressure, and the residue was dissolved in methanol (200 mL). The solution was cooled with an ice/water bath to 0° C., and then 4-methylbenzenesulfonic acid hydrate (2.43 g, 15.4 mmol) was added in one portion. The resulting solution was stirred at 25° C. for 18 hours. LC-MS showed the reaction was complete. Saturated aqueous sodium bicarbonate (50 mL) was added, and the mixture was concentrated under reduced pressure to remove most of the methanol. The residue was treated with water (100 mL) and ethyl acetate (100 mL), the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure to give crude product 56 as a white solid (8.0 g, 89.6% yield), which was used for the next step without further purification.

Provenance & Evidence