Tetrahydrofuran → HCID 5358230, compound

Participants

Reaction Conditions

Reaction Steps

Ansamitocins (3.0 g, 4.72 mmol) were weighed into a three necked flask equipped with a thermometer. Tetrahydrofuran (15 mL) was added to the flask with stirring and the flask was cooled in a −50° C. cooling bath. Once the contents of the flask reached −35° C., a solution of 0.67 M LiAl(OMe)3H in tetrahydrofuran (56 mL, 37.7 mmol) was added dropwise by syringe using a syringe pump. The temperature of the reaction was maintained between −30° C. and −40° C. throughout the addition. After addition was complete, the reaction was stirred for 2 hours at between −32° C. and −37° C. Deionized water (7.7 mL) was added dropwise to the −35° C. reaction to give a basic quenched mixture. The basic quenched mixture was analyzed after set holding periods by the thin layer chromatography assay described in Example 6. The compound of Formula (I) was detected after holding for 5 and 15 minutes. After 30 min a sample of the basic quenched mixture was analyzed again by the thin layer chromatography method. The compound of Formula (I) was no longer detected. Aqueous formic acid (deionized water, 15 mL and 88% formic acid, 1.85 mL) was then added to the flask followed by 66 mL of ethyl acetate. The cooling unit was turned off, and the mixture was allowed to slowly warm to room temperature. The pH of the mixture was checked with pH paper and found to be approximately pH 6. The precipitated aluminum byproducts were removed by vacuum filtration. Solvent was evaporated from the filtrate by rotary evaporation under vacuum. Butyl acetate was added to the residue, the solvent was then evaporated to remove any remaining water The residue was purified by silica chromatography using a mobile phase of dichloromethane:methanol 95:5 (v:v) to give 2.2 g of maytansinol (85% yield by weight).

Provenance & Evidence