Ammonium Hydroxide → 3-[2-[2-(Aminomethyl)-4-thiazolyl]-1-methylethenyl]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of epothilone F (10 g, 19.1 mmol) in tetrahydrofuran (200 ml) under argon, chilled in an ice bath to 5° C. or below, was added diphenylphosphoryl azide (6.20 ml, 7.90 g, 28.6 mmol, 1.5 equivalents). The mixture was stirred for approximately 10 min. 1,8-diazabicyclo[5.4.0]undec-7-ene (3.43 ml, 3.53 g, 22.8 mmol, 1.2 equivalents) was then added gradually at a rate that maintained the temperature of the mixture below 8° C. The mixture was stirred for 30 min., then allowed to warm to 20° C. and stirred for 18 hours. To the reaction mixture was added a solution of 1.0 M trimethylphosphine in tetrahydrofuran (21 ml, 18.3 g, 21 mmol, 1.1 equivalents), which generated a mild exotherm with gas evolution. The mixture was allowed to stir at 20° C. for 30 minutes, and water (52 ml) was added. After 30 minutes, 28% aqueous NH4OH (26.5 ml) was added. After stirring at 25° C. for another 30 minutes, water (100 ml) was added, and the mixture was extracted with methylene chloride (3×100 ml). The combined organic extracts were washed with 1.0 M aqueous ammonium hydroxide (2×100 ml), and then with half-saturated aqueous sodium chloride (100 ml). The solvents were removed on a rotary evaporator, and the residue dried in vacuo for 18 hours.

Provenance & Evidence