tert-Butyl acetate → (3-Chloro-isoquinolin-1-yl)-acetic acid tert.-butyl ester

HRID 493732

반응식

HRID 493732 반응식
[C:1]([O:5][C:6](=[O:8])[CH3:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[C:12]([Cl:20])[N:11]=1>>[C:1]([O:5][C:6](=[O:8])[CH2:7][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[C:12]([Cl:20])[N:11]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

3

반응물 2

HCID 10908tert-Butyl acetateHCID 2986251,3-Dichloroisoquinoline

생성물 1

HCID 86598360(3-Chloro-isoquinolin-1-yl)-acetic acid tert.-butyl ester

실험 절차

After stirring at RT for 10 minutes, the clear dark red solution is cooled to −10° C. Acetic acid tert-butyl ester (15.7 ml, 13.5 g, 116.1 mmol) is added during 5 min. After 10 minutes at −10° C., 1,3-Dichloro-isoquinoline (10.0 g, 50.49 mmol) is added in one portion. The dark red solution is allowed to warm to RT. After 30 minutes at RT, TLC analysis indicates complete conversion of the starting material. The reaction mixture is filtered through a 2-cm pad of silica, which is rinsed with EtOAc/MeOH 98:2. After concentration, the residue is purified by FCC (toluene/CH2Cl2 2:1 to toluene/EtOAc 100:0 to 99:1 to 98:2 to 97:3 to 96:4 to 94:6 to 90:10) to afford (3-Chloro-isoquinolin-1-yl)-acetic acid tert.-butyl ester. This compound is dissolved in a saturated ethanolic solution of HCl (200 ml) and refluxed for 15 minutes. Concentration affords the title compound in quantitative yield. 1H NMR (DMSO, 400 MHz) δ 1.17 (t, J=8.8, 3H), 4.11 (q, J=8.8, 2H), 4.28 (s, 2H), 7.51-7.57 (m, 1H), 7.61 (s, 1H), 7.61-7.66 (m, 1H), 7.72 (d, J=8.8, 1H), 7.98 (d, J=8.8, 1H); ES-MS: 250 [M+H]+.

후처리

  1. temperaturethe clear dark red solution is cooled to −10° C
  2. waitAfter 10 minutes at −10° C.
  3. temperatureto warm to RT
  4. waitAfter 30 minutes at RT
  5. filtrationThe reaction mixture is filtered through a 2-cm pad of silica, which
  6. washis rinsed with EtOAc/MeOH 98:2
  7. concentrationAfter concentration
  8. customthe residue is purified by FCC (toluene/CH2Cl2 2:1 to toluene/EtOAc 100:0 to 99:1 to 98:2 to 97:3 to 96:4 to 94:6 to 90:10)

출처 및 근거

ORD 기록
ord-c892901c486348b5b641ec6a81d6d6c5
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07534808B2

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