Sodium hydride → methyl 6-bromo-1-cyclobutyl-1H-indole-4-carboxylate

HRID 42513노트

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HRID 42513 반응식
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][NH:8][C:9]=2[CH:10]=1.[Cl-].C(C[P+](C)(C)C)#N.[CH:23]1(O)[CH2:26][CH2:25][CH2:24]1.[H-].[Na+]>C1COCC1.CCOC(C)=O.CCCCCC>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][N:8]([CH:23]3[CH2:26][CH2:25][CH2:24]3)[C:9]=2[CH:10]=1

참가 물질

8

반응물 4

HCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 13770009methyl 6-bromo-1H-indole-4-carboxylateHCID 57431663(Cyanomethyl)trimethylphosphonium chloride

생성물 1

HCID 67469195methyl 6-bromo-1-cyclobutyl-1H-indole-4-carboxylate수율 25%

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매HCID 8058Hexane용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

In an oven dried 100 ml RBF, equipped with a stir bar, septum, nitrogen inlet was added methyl 6-bromo-1H-indole-4-carboxylate (1.0 g, 3.94 mmol) and (cyanomethyl)(trimethyl)phosphonium chloride (1.491 g, 9.84 mmol). Added in THF (40 mL) and stirred suspension for 5 min. The reaction was cooled with an ice bath for 10 min, then was added cyclobutanol (0.616 mL, 7.87 mmol), followed by sodium hydride (0.346 g, 8.66 mmol) portionwise. The ice bath was removed and the reaction stirred at ambient temperature for 45 min, then heated at 50° C. for 18 h. LCMS showed mostly SM. Heated at 75° C. for 24 h. The reaction was allowed to cool to RT, then poured into water (200 ml) and extracted with EtOAc (2×). The combined organics were dried over magnesium sulfate, filtered, and concentrated. Purification of the residue by column chromatography (40 g Isco silica column; gradient B: 2-25%; A:hexane, B: EtOAc) gave methyl 6-bromo-1-cyclobutyl-1H-indole-4-carboxylate (0.3 g, 25% yield, ˜45% pure by HPLC). MS (ES) [M+H]+ 308.2.

후처리

  1. customIn an oven dried 100 ml RBF
  2. customequipped with a stir bar
  3. temperatureThe reaction was cooled with an ice bath for 10 min
  4. customThe ice bath was removed
  5. stirringthe reaction stirred at ambient temperature for 45 min
  6. temperatureHeated at 75° C. for 24 h
  7. temperatureto cool to RT
  8. additionpoured into water (200 ml)
  9. extractionextracted with EtOAc (2×)
  10. dry with materialThe combined organics were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification of the residue by column chromatography (40 g Isco silica column

출처 및 근거

ORD 기록
ord-502335e0c34d47f4ac229537e90190e9
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536179B2

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