Potassium Carbonate → racemic {1-methyl-2-[7-cyanomethoxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester

HRID 1272218

반응식

HRID 1272218 반응식
[C:1]([O:5][C:6](=[O:28])[NH:7][CH:8]([CH3:27])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([O:19][CH2:20][C:21]3C=CC=CC=3)[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].BrCC#[N:32].C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][CH:8]([CH3:27])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([O:19][CH2:20][C:21]#[N:32])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 11485811{1-Methyl-2-[7-(benzyloxy)-1h-indol-3-yl]ethyl}-carbamic acid tert-butyl ester

생성물 1

HCID 69518565racemic {1-methyl-2-[7-cyanomethoxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester수율 70.2%

시약·촉매·용매 1

HCID 6569Methyl Ethyl Ketone용매

반응 조건

온도
80 °C

실험 절차

The crude {1-methyl-2-[7-hydroxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester from above (29.2 g, 102 mmol theory) is dissolved in methyl ethyl ketone (300 mL) and bromoacetonitrile (20.4 mL, 306 mmol) and potassium carbonate (33.8 g, 250 mmol) is added. The mixture is heated at 80° C. for 2 hours. The solids are removed by filtration, the cake is washed with methyl ethyl ketone, and the combined filtrates are concentrated by rotary evaporation. The crude product is purified by flash chromatography (500 g silica gel, eluted with 8×500 mL dichloromethane, 4×500 mL 5% ethyl acetate/dichloromethane, 6×500 mL 10% ethyl acetate/dichloromethane). The fractions containing product are concentrated and hexane is added to the solution to precipitate out the product affording 23.7 g (70.2% yield) of racemic {1-methyl-2-[7-cyanomethoxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester.

후처리

  1. customThe solids are removed by filtration
  2. washthe cake is washed with methyl ethyl ketone
  3. concentrationthe combined filtrates are concentrated by rotary evaporation
  4. customThe crude product is purified by flash chromatography (500 g silica gel, eluted with 8×500 mL dichloromethane, 4×500 mL 5% ethyl acetate/dichloromethane, 6×500 mL 10% ethyl acetate/dichloromethane)
  5. additionThe fractions containing product
  6. concentrationare concentrated
  7. additionhexane is added to the solution
  8. customto precipitate out the product

출처 및 근거

ORD 기록
ord-e7d1f6f67edb4d0680b5b52bb53965a8
출처 데이터셋
uspto-grants-2007_04
특허 번호
US07208505B2

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