Sodium hydride → 1,1-dimethylethyl 5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 2059924ノート

反応式

HRID 2059924 の反応式
[OH:1][NH:2][C:3](=[NH:21])[C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2.[H-].[Na+].[Cl:24][C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=1[O:35][CH:36]([CH3:38])[CH3:37])[C:28](OC)=O>O1CCCC1>[Cl:24][C:25]1[CH:26]=[C:27]([C:28]2[O:1][N:2]=[C:3]([C:4]3[CH:13]=[CH:12][CH:11]=[C:10]4[C:5]=3[CH2:6][CH2:7][N:8]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:9]4)[N:21]=2)[CH:32]=[CH:33][C:34]=1[O:35][CH:36]([CH3:37])[CH3:38]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 22597811Methyl 3-chloro-4-isopropoxybenzoateHCID 178451585HCID 178451585、化合物

生成物 1

HCID 593704861,1-dimethylethyl 5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate収率 80%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

1,1-dimethylethyl 5-[(hydroxyamino)(imino)methyl]-3,4-dihydro-2(1H)-isoquinoline carboxylate (Preparation 1)(2 g, 6.86 mmol) was dissolved in tetrahydrofuran (THF) (100 mL) and stirred with sodium hydride (60% dispersion, 0.302 g, 7.55 mmol) under argon at room temperature for 30 minutes. Then methyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (Preparation 2)(2.355 g, 10.30 mmol) was added and the reaction heated at reflux temperature for 1.5 hours. The cooled reaction was evaporated and partitioned between DCM (100 mL) and water (100 mL). The water layer was washed with DCM (50 mL) and the combined DCM layers dried (hydrophobic frit) and evaporated. The crude product was purified by chromatography through a small silica pad, eluting with DCM to yield 1,1-dimethylethyl 5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinoline carboxylate (2.57 g, 5.47 mmol, 80% yield). 1H NMR (400 MHz, CDCl3) δ 8.23 (1H, s), 8.05 (1H, d), 7.95 (1H, d), 7.34 (1H, t), 7.27 (1H, d), 7.06 (1H, d), 4.76-4.63 (1H, m), 4.66 (2H, br.s), 3.67 (2H, br.t), 3.25 (2H, br.t), 1.51 (9H, s), 1.45 (6H, d); m/z (API-ES) 414, 416 [M+H-56]+.

後処理

  1. temperaturethe reaction heated
  2. temperatureat reflux temperature for 1.5 hours
  3. customThe cooled reaction
  4. customwas evaporated
  5. custompartitioned between DCM (100 mL) and water (100 mL)
  6. washThe water layer was washed with DCM (50 mL)
  7. dry with materialthe combined DCM layers dried (hydrophobic frit)
  8. customevaporated
  9. customThe crude product was purified by chromatography through a small silica pad
  10. washeluting with DCM

出典と根拠

ORDレコード
ord-453de59988f549868a008fbecac89128
出典データセット
uspto-grants-2012_10
特許番号
US08278324B2

反応ノート

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