Triethylamine → Discodermolide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2.18 g (6.79 mmol, 10 equiv.) of (+)-β-chlorodiisopinocamphenylborane in 4 mL of diethyl ether at 0° C. is added 1.04 mL (11 equiv., distilled over calcium hydride) of triethylamine and then a solution of 2.25 g (6.79 mmol, 10 equiv.) of the compound of Example 1 in 3 mL of diethylether. After stirring for 2 hours at 0° C., the mixture is cooled to −78° C., after which time a pre-cooled (−78° C.) solution of 450 mg (0.679 mmol) of (2Z,4S,5S,6S,7Z,10S,11R,12R,13S,14S,15E)-13-[(amino-carbonyl)oxyl]-5,11-bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-4,6,8,10,12,14-hexamethyl-2,7,15,17-octadecatetraenal in 4 mL of diethylether is added via cannula. After the resultant mixture is maintained at a temperature of −78° C. for 3 hours, it is transferred to a freezer (−27° C.) for 16 hours. The reaction is then quenched with 8 mL of methanol (the pH of which is adjusted to 7 with 12 mL of buffer solution) and 4 mL of 50% hydrogen peroxide solution at 0° C. After stirring for 2 hours at 25° C., the organic layers are separated. The aqueous layer is then extracted five times with 25 mL portions of dichloromethane. The combined organic layers are then dried over magnesium sulfate, concentrated using a rotary evaporator and chromatographed (Biotage, silica gel, gradient 10-30% ethyl acetate/hexane) to yield the desired compound as a colorless, highly viscous oil.

Provenance & Evidence