Hydrochloric Acid → 1-Methylindole

HRID 6709

반응식

HRID 6709 반응식
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:10](OC)(=O)C(OC)=O.CC(C)([O-])C.[K+].Cl>CN(C=O)C.O.C(OCC)C>[CH3:10][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 798IndoleHCID 11120Dimethyl oxalateHCID 23665647Potassium tert-butoxide

생성물 1

HCID 117811-Methylindole수율 95.3%

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

The indole product from Example 56 (100 mg, 0.36 mmol) and dimethyl oxalate (46 mg, 0.39 mmol) in DMF (3 mL) were treated with potassium t-butoxide (44 mg, 0.39 mmol). The reaction was heated at reflux for 30 min. Reaction was cooled to room temperature and diluted with water (25 mL). Following extractions (3×) with ethyl acetate, the organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated. The dark residue was chromatographed (SiO2, 20% EtOAc/hexanes), and the resulting oil was treated with 1 M HCl (1 eq) in diethyl ether to provide the N-methyl indole product as a white solid (45 mg, 11%): mp 255-258° C.; 1H NMR (300 MHz, CD3OD) δ 7.43-7.25 (m, 3H), 7.12-7.00 (m, 2H), 6.99 (d, J=10.0 Hz, 1H), 6.70 (d, J=8.6 Hz, 1H), 6.50 (d, J=3.1 Hz, 1H), 4.80-4.67 (m, 2H), 3.89 (dd, J=5.6, 11.9 Hz, 1H), 3.81 (s, 3H), 3.65-3.55 (m, 1H), 3.30-3.29 (m, 1H), 3.14 (s, 3H); IR (KBr) 3424, 2944, 2479, 1590, 1449 cm−1; CI MS m/z=295 [C19H19FN2+H]+.

후처리

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 30 min
  3. customReaction
  4. extractionextractions (3×) with ethyl acetate
  5. washthe organic layers were washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe dark residue was chromatographed (SiO2, 20% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-ccc6e315b0734760bd2eddf77c0f3649
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07084152B2

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