Borane;tetrahydrofuran → 7-[(1R)-2-Azido-1-hydroxy-ethyl]-4-hydroxy-3H-benzothiazol-2-one

Participants

Reaction Conditions

Reaction Steps

(1R,2S)-(+)-cis-1-Amino-2-indanol (149 g) was added portion wise to borane-tetrahydrofuran complex (1M in tetrahydrofuran, 2997 mL) over 25 minutes maintaining a temperature of 20-25° C. The mixture was stirred at 20° C. for a further 30 minutes, cooled to 0° C. and 7-(2-azido-acetyl)-4-hydroxy-3H-benzothiazol-2-one (example 1, step b) (250 g) added portionwise maintaining the temperature 0-5° C. The reaction mixture was stirred for a further 1 h at 0° C. and then quenched dropwise with methanol (350 g, 442 mL) (caution effervescence!). An exotherm brought the temperature to 17° C. The reaction was evaporated to a brown foam and re-dissolved in ethyl acetate (1.2 L). Aqueous hydrochloric acid (87 mL conc. HCl in 1.2 L water) was added and the mixture stirred vigorously for 30 minutes. The aqueous layer was separated and washed with fresh ethyl acetate (2×600 mL). The combined organic solution was washed with water (1.2 L). The aqueous layer was filtered through Celite and extracted with ethyl acetate (600 mL). The ethyl acetate solutions were combined, dried over Na2SO4, filtered and evaporated. The resulting solid was suspended in 5% ethanol/dichloromethane (2 L), stirred for 3 h, filtered and dried in vacuo to give the subtitled compound. Yield 213 g.

Provenance & Evidence