Formic Acid → (S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol

HRID 2170924노트

반응식

HRID 2170924 반응식
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:12].C(O)=O.C(N[C@H](C(O)=O)CS)(=O)C.Cl>O.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@@H:6]2[OH:12]

참가 물질

7

반응물 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 12035N-Acetyl-L-CysteineHCID 534401624-Bromo-7-fluoroindan-1-one

생성물 1

HCID 86697104(S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매2회

반응 조건

온도
40 °C

실험 절차

20.0 g (87.3 mmol) 4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-one, 142 ml toluene and 13.9 g (138 mmol) TEA are added into a vessel. The mixture is degassed and heated to 40° C. Then, 272 mg (0.44 mmol) chloro{[(1S,2S)-(−)-2-amino-1,2-diphenylethyl](4-toluenesulfonyl)amido}-(mesitylene)ruthenium(II) is added before a mixture of 7.03 g (153 mmol) formic acid (98%) and 3.00 mL toluene is added over a time period of 60 min. The funnel is rinsed with 7.00 ml toluene. Stirring is continued at 40° C. for approx. 90 min until full conversion (HPLC). 1.43 g (8.73 mmol) N-acetyl-L-cystein is added and stirring is continued for 30 min. A mixture of 15.8 g (160 mmol) conc. HCl in 24 ml water is added and the aqueous phase is separated. The organic phase is washed with 35.0 ml water and 140 ml solvent is distilled off. 90 ml IPA is added and 70 ml solvent is distilled off. To the residue 50 ml water is added and the mixture is cooled to 35° C. Then, seeds are added followed by 50 ml water. The suspension is cooled to 22° C. and stirred for 2 h. The product is filtered off, washed with water (2×30 ml) and dried. Yield: 18.6 g; LC (method 1): tR=0.91 min; Mass spectrum (ESI+): m/z=213 [M+H—H2O]+.

후처리

  1. customThe mixture is degassed
  2. additionis added over a time period of 60 min
  3. washThe funnel is rinsed with 7.00 ml toluene
  4. stirringstirring
  5. waitis continued for 30 min
  6. additionis added
  7. customthe aqueous phase is separated
  8. washThe organic phase is washed with 35.0 ml water and 140 ml solvent
  9. distillationis distilled off
  10. addition90 ml IPA is added
  11. distillation70 ml solvent is distilled off
  12. additionTo the residue 50 ml water is added
  13. temperaturethe mixture is cooled to 35° C
  14. additionThen, seeds are added
  15. temperatureThe suspension is cooled to 22° C.
  16. stirringstirred for 2 h
  17. filtrationThe product is filtered off
  18. washwashed with water (2×30 ml)
  19. customdried

출처 및 근거

ORD 기록
ord-34033d35d9a44c298cdf6654a9eb6887
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051289B2

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