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

HRID 493732

反応式

HRID 493732 の反応式
[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]

参加物

3

反応物 2

HCID 10908tert-Butyl acetateHCID 2986251,3-Dichloroisoquinoline

生成物 1

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

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-c892901c486348b5b641ec6a81d6d6c5
出典データセット
uspto-grants-2009_05
特許番号
US07534808B2

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