Boron trifluoride etherate → HCID 118021648, compound

Participants

Reaction Conditions

Reaction Steps

To a 20 L temperature controlled reactor charge [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[(4-bromophenyl)-hydroxy-methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate (1492.5 g; 65% purity; 1.506 moles), then acetonitrile (4.87 L), and then dichloromethane (4.87 L). Cool the mixture to 0° C. Add triethylsilane (3.77 moles; 437.83 g) over 5 minutes. Set the reactor jacket to −5° C. When the reaction mixture temperature is −2° C., start addition of boron trifluoride etherate (3.77 moles; 534.4 g). Note: at the start, this addition results in a significant exotherm (temperature increases to ˜8° C. during the first ˜10 ml of addition). Once the initial exothermic event has taken place, add the remainder of the boron trifluoride etherate at a rate to maintain the temperature between 5° C. and 7° C. When the addition is complete stir the reaction mixture at 5° C. for 50 minutes. Charge a 50 L glass flask equipped with a bottom outlet valve with ice (6 kg), and then water (˜15 C; 3.74 Kg). Add sodium bicarbonate (11.16 moles; 937.55 g) and stir the mixture for 5 minutes. Pump the reaction mixture into the sodium bicarbonate mixture over about 5 minutes. A little effervescence is seen, but no tendency to foam. Add ethyl acetate (17.04 L) and stir the mixture for 10 minutes. Stop the stiffing and allow the mixture to stand for 30 minutes. Separate the layers, wash the organic phase with brine (4.87 L), and concentrate under reduced pressure. Split the mixture into two approximately equal portions and purify each by passage through a 4.5 Kg pad of silica eluting with dichloromethane. Concentrate the appropriate fractions to give the title compound (990 g, about 70% purity (as determined by quantative NMR; 73% yield from [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-(4-bromobenzoyl)-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate): mass spectrum (m/z): 630.2/632.2 (M+1).

Provenance & Evidence