Ethyl Acetate → Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate

HRID 2388176ノート

反応式

HRID 2388176 の反応式
Br[CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[N:5][O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:20]([O:22][C:23](=[O:37])[CH2:24][NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=1[O:35][CH3:36])[CH3:21].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>CN(C=O)C.[Cl-].[Na+].O>[CH3:36][O:35][C:28]1[CH:29]=[C:30]([O:33][CH3:34])[CH:31]=[CH:32][C:27]=1[CH2:26][N:25]([CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[N:5][O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:24][C:23]([O:22][CH2:20][CH3:21])=[O:37]

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 19895532Ethyl 2-(2,4-dimethoxybenzylamino)acetateHCID 67529002Ethyl 4-(bromomethyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate

生成物 1

HCID 67530684Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate収率 46%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

Ethyl 4-(bromomethyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate (12.4 g, 37.8 mmol) was dissolved in 80 mL of DMF. N-(2,4-dimethoxybenzyl)glycine ethyl ester (9.56 g, 37.8 mmol) and potassium carbonate (5.75 g, 41.6 mmol) were added, and the mixture was stirred at room temperature for 16 h. EtOAc (200 mL) and brine (200 mL) were added and the aqueous layer was extracted with additional EtOAc. The combined organic layer was washed with water and brine, and dried over MgSO4. After solvent was removed in vacuo, the crude product was purified by flash chromatography (0-40% EtOAc/hexanes) to give 8.7 g of the title compound. 1H NMR (CDCl3, 200 MHz): δ=8.00-8.13 (m, 2H), 7.01-7.18 (m, 3H), 6.38-6.45 (m, 2H), 4.48 (q, 2H, J=7.4 Hz), 4.00-4.20 (m, 4H), 3.82 (s, 5H), 3.65 (s, 3H), 3.30 (s, 2H), 1.47 (t, 3H, J=7.0 Hz), 1.20-1.30 (m, 3H).

後処理

  1. extractionthe aqueous layer was extracted with additional EtOAc
  2. washThe combined organic layer was washed with water and brine
  3. dry with materialdried over MgSO4
  4. customAfter solvent was removed in vacuo
  5. customthe crude product was purified by flash chromatography (0-40% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-5b3995b2089947a8b854d1caa01a6bce
出典データセット
uspto-grants-2012_09
特許番号
US08269008B2

反応ノート

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