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

HRID 1987574

반응식

HRID 1987574 반응식
C[O:2][C:3](=O)[C@@H:4]([NH:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)(=[O:19])=[O:18])[CH:5]([CH2:11][C:12]([F:15])([F:14])[F:13])[CH2:6][C:7]([F:10])([F:9])[F:8].[Li+].[BH4-]>C1COCC1.CCOC(C)=O.CCCCCCC>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([NH:16][C@H:4]([CH2:3][OH:2])[CH:5]([CH2:6][C:7]([F:8])([F:9])[F:10])[CH2:11][C:12]([F:14])([F:13])[F:15])(=[O:18])=[O:19])=[CH:21][CH:22]=1

참가 물질

6

반응물 2

HCID 4148881Lithium borohydride2회HCID 25112113(2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)pentanoic acid methyl ester

생성물 1

HCID 575292724-chloro-N-[(1S)-4,4,4-trifluoro-1-hydroxymethyl-2-(2,2,2-trifluoroethyl)-butyl]benzenesulfonamide수율 72%

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 8900Heptane용매2회

반응 조건

온도
25 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c2234b2e0ba7425c9d0b24bcafb64eed
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07550629B2

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