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

Temperature

22.5 °C

(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.

1. temperaturecooled to 0° C.
2. temperaturemaintaining the temperature 0-5° C
3. stirringThe reaction mixture was stirred for a further 1 h at 0° C.
4. customquenched dropwise with methanol (350 g, 442 mL) (caution effervescence!)
5. customto 17° C
6. customThe reaction was evaporated to a brown foam
7. dissolutionre-dissolved in ethyl acetate (1.2 L)
8. additionAqueous hydrochloric acid (87 mL conc. HCl in 1.2 L water) was added
9. stirringthe mixture stirred vigorously for 30 minutes
10. customThe aqueous layer was separated
11. washwashed with fresh ethyl acetate (2×600 mL)
12. washThe combined organic solution was washed with water (1.2 L)
13. filtrationThe aqueous layer was filtered through Celite
14. extractionextracted with ethyl acetate (600 mL)
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. customevaporated
18. stirringstirred for 3 h
19. filtrationfiltered
20. customdried in vacuo

ORD record

ord-460b2c2634fa4d7ba28c2a6bcd52bf19

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148373B2