HCID 99958, compound → HCID 5358230, compound

Temperature

-50 °C

This example describes reduction of ansamitocins with LiAl(OMe)2.5H1.5 using water followed by aqueous formic acid quench. Ansamitocins (1.0 g, 1.57 mmol) were weighed into a three necked flask equipped with a thermometer. Tetrahydrofuran (5 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 (18.5 mL, 12.4 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 (2.5 mL) was added dropwise to the −35° C. reaction to give a basic quenched mixture. The basic quenched mixture was analyzed by the thin layer chromatography assay described in example 6. The compound of Formula (I) was detected. After 30 min 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, 5 mL, and 88% formic acid, 0.62 mL) was then added to the flask followed by 22 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 mixture was vacuum filtered, and solvent was removed by rotary evaporation under vacuum. Butyl acetate (5 mL) 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 0.63 g of maytansinol (71% yield by weight).

1. customquench
2. customequipped with a thermometer
3. temperaturecooling bath
4. customreached −35° C.
5. temperatureThe temperature of the reaction was maintained between −30° C. and −40° C. throughout the addition
6. additionAfter addition
7. stirringwas stirred for 2 hours at between −32° C. and −37° C
8. customto give a basic
9. customquenched mixture
10. customThe basic quenched mixture
11. customAfter 30 min the basic quenched mixture
12. additionAqueous formic acid (deionized water, 5 mL, and 88% formic acid, 0.62 mL) was then added to the flask
13. temperatureto slowly warm to room temperature
14. filtrationfiltered
15. customsolvent was removed by rotary evaporation under vacuum
16. additionButyl acetate (5 mL) was added to the residue
17. customthe solvent was then evaporated
18. customto remove any remaining water
19. customThe residue was purified by silica chromatography

ORD record

ord-4232c924ce964610a4947e471b76edad

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07411063B2