Lithium borohydride → 4-chloro-N-[(1S)-4,4,4-trifluoro-1-hydroxymethyl-2-(2,2,2-trifluoroethyl)-butyl]benzenesulfonamide

温度

25 °C

To a solution of (2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)pentanoic acid methyl ester (2.924 g, 6.6 mmol) in THF (30 mL) was added LiBH4 (9.9 mL of 2M THF solution, 19.8 mmol) over 10 min at 4-6° C. The reaction mixture was stirred at 25° C. for 4 days. Additional LiBH4 (6.6 mL of 2M THF solution, 13.2 mmol) was added and the reaction mixture was stirred at 25° C. for an additional 24 h. The reaction mixture was cooled to 0° C. and quenched by slow addition of 30 mL of 2N HCl (vigorous gas evolution). The mixture was partially concentrated in vacuum and extracted with EtOAc. The organic fraction was washed with brine, dried over Na2SO4, and concentrated to afford 2.66 g of crude product. The crude product was dissolved in a mixture of EtOAc (10 mL) and heptane (3 mL) at 55° C., cooled to 25° C., and the resultant suspension was aged for 48 h. Heptane (27 mL) was added, and the mixture was stirred at 25° C. for additional 48 h. The precipitate was filtered, and washed with heptane to afford 1.962 g of the title compound (72% yield), mp: 186-187° C. Chiral HPLC: 97% ee (Chiralcel® AD column 0.46×25 cm, 10% EtOH in hexanes) HRMS calc. (for M+H): 414.0360; found: 414.0359.

1. stirringthe reaction mixture was stirred at 25° C. for an additional 24 h
2. temperatureThe reaction mixture was cooled to 0° C.
3. customquenched by slow addition of 30 mL of 2N HCl (vigorous gas evolution)
4. concentrationThe mixture was partially concentrated in vacuum
5. extractionextracted with EtOAc
6. washThe organic fraction was washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customto afford 2.66 g of crude product
10. temperaturecooled to 25° C.
11. stirringthe mixture was stirred at 25° C. for additional 48 h
12. filtrationThe precipitate was filtered
13. washwashed with heptane

ORDレコード

ord-c2234b2e0ba7425c9d0b24bcafb64eed

出典データセット

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07550629B2