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Sodium hydride → 1,1-Dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 1514187
ノート
印刷プレビュー

反応式

HRID 1514187 の反応式
[OH:1][NH:2][C:3](=[NH:22])[C:4]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.[H-].[Na+].[Cl:25][C:26]1[CH:27]=[C:28]([CH:33]=[CH:34][C:35]=1[O:36][CH:37]([CH3:39])[CH3:38])[C:29](OC)=O>C1COCC1>[Cl:25][C:26]1[CH:27]=[C:28]([C:29]2[O:1][N:2]=[C:3]([C:4]3[C:14]4[CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10][CH2:9][C:8]=4[CH:7]=[CH:6][CH:5]=3)[N:22]=2)[CH:33]=[CH:34][C:35]=1[O:36][CH:37]([CH3:38])[CH3:39]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 22597811Methyl 3-chloro-4-isopropoxybenzoateHCID 178451587HCID 178451587、化合物

生成物 1

HCID 594034711,1-Dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

1,1-dimethylethyl 6-[(hydroxyamino)(imino)methyl]-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (Preparation 15) (170 mg, 0.557 mmol) was dissolved in THF (30 ml) and stirred with sodium hydride (24.49 mg, 0.612 mmol) under argon at room temperature for 30 minutes. Then methyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (may be prepared as described in WO2005058848) (191 mg, 0.835 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 title compound was isolated by silica chromatography (eluting with DCM). 1,1-dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (260 mg, 0.537 mmol, 96% yield) was isolated as an off-white foam. δH (400 MHz, CDCl3) 8.22 (1H, s), 8.05 (1H d), 7.68 (1H, d), 7.30-7.24 (2H, m), 7.06 (1H, d), 4.72 (1H, sept), 3.65-3.55 (4H, m), 3.35-3.25 (2H, m), 2.95-3.05 (2H, m); 1.45 (6H, d), 1.43 (9H, s); MS (ES) C26H3035ClN3O4 requires 483; found 484 [M+H]+.

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

出典と根拠

ORDレコード
ord-3301ed6ade5b43e08bde70f702ece6e4
出典データセット
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08222245B2

反応ノート

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