Sulfuryl chloride → Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

HRID 913387노트

반응식

HRID 913387 반응식
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2.S(Cl)([Cl:24])(=O)=O>C1(C)C=CC=CC=1.C(N)(C)(C)C.S(Cl)(Cl)(=O)=O>[Cl:24][C:3]1[C:2]([OH:1])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:7]2[CH2:11][C:12]([F:15])([F:13])[F:14]

참가 물질

6

반응물 2

HCID 24648Sulfuryl chloride2회HCID 24985291Ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

생성물 1

HCID 57800334Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate수율 92%

시약·촉매·용매 3

HCID 6385Tert-Butylamine촉매3회HCID 24648Sulfuryl chloride촉매HCID 1140Toluene용매2회

실험 절차

To a solution of ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate (0.7 g, 2.44 mmol) in toluene (30 mL) was added tert-butyl amine (0.014 g, 0.2 mmol) and the mixture was set in an oil bath preheated at 70° C. After 1 min, a solution of sulfuryl chloride (0.37 g, 2.49 mmol) in toluene (1 mL) was added. The reaction was followed by TLC (60% CH2Cl2-hexanes) and additional reagents were added accordingly. After 30 min, more tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.06 g, 0.37 mmol) were added. After another 30 min additional tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.019 g, 0.12 mmol) were added and heating was continued for 30 min. Upon cooling, the mixture was partitioned between EtOAc and 0.2N HCl. The organic phase was washed with 0.2N HCl and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient) to afford the title compound (0.72 g, 92% yield, 95% purity): MS (ES) m/z 322 (M+1).

후처리

  1. customthe mixture was set in an oil bath
  2. custompreheated at 70° C
  3. additionwere added accordingly
  4. waitAfter 30 min
  5. temperatureheating
  6. waitwas continued for 30 min
  7. temperatureUpon cooling
  8. customthe mixture was partitioned between EtOAc and 0.2N HCl
  9. washThe organic phase was washed with 0.2N HCl
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient)

출처 및 근거

ORD 기록
ord-31285f029ba842bca21d6e1fa4f03c41
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026262B2

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