2-Methyl-2-butene → 5-{4-[1-(tert-butoxycarbonyl)pyrrolidin-2-yl]phenyl}-6-chloro-1H-indole-3-carboxylic acid

HRID 1054767노트

반응식

HRID 1054767 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:37].[Na+].P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.O.C(O)(C)(C)C>[C:27]([O:26][C:24]([N:20]1[CH2:21][CH2:22][CH2:23][CH:19]1[C:16]1[CH:17]=[CH:18][C:13]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[NH:8][CH:7]=[C:6]3[C:11]([OH:37])=[O:12])=[CH:14][CH:15]=1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

참가 물질

9

반응물 5

HCID 105532-Methyl-2-buteneHCID 24243Trisodium PhosphateHCID 24437Sodium SulfiteHCID 23668197Sodium ChloriteHCID 86698758tert-butyl 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate

생성물 1

HCID 866987595-{4-[1-(tert-butoxycarbonyl)pyrrolidin-2-yl]phenyl}-6-chloro-1H-indole-3-carboxylic acid수율 84.2%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6342Acetonitrile용매HCID 6386tert-Butanol용매

반응 조건

온도
0 °C

실험 절차

The tert-butyl 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate (160 mg, 0.377 mmol) was dissolved in acetonitrile (9 mL) and warm t-butanol (9 mL) followed by the addition of 2-methyl-2-butene (6.00 mL, 56.5 mmol) and cooled to 0° C. followed by the addition of an aqueous solution of sodium chlorite (763 mg, 11.3 mmol) and sodium phosphate (monobasic and monohydrate, 1.56 g, 11.3 mmol) in water (5 mL) dropwise via additional funnel. The ice bath was removed and the mixture was allowed to warm to room temperature. The suspension was stirred overnight. To the suspension was added sodium sulfite (1.43 g, 11.3 mmol) in water (3 mL) and the resultant mixture concentrated to remove the organic solvent followed by extraction three times with ethyl acetate (15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to afford crude product which was purified by reverse phase HPLC to afford the title compound (140 mg, 84.2% yield).

후처리

  1. customThe ice bath was removed
  2. temperatureto warm to room temperature
  3. concentrationthe resultant mixture concentrated
  4. customto remove the organic solvent
  5. extractionfollowed by extraction three times with ethyl acetate (15 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford crude product which
  10. customwas purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-bc5f56fccfeb45f9b2b7372754418179
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394285B2

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