Sodium Bicarbonate → tert-butyl (3S)-3-({4-[4-(1-benzofuran-5-yl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)pyrrolidine-1-carboxylate

HRID 525166ノート

反応式

HRID 525166 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][N:10]=[C:9]2[CH2:14][C@@H:15]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]3[O:42][CH:41]=[CH:40][C:39]=3[CH:43]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.C(OCC)(=O)C>[O:42]1[C:38]2[CH:37]=[CH:36][C:35]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12](=[O:13])[NH:11][N:10]=[C:9]4[CH2:14][C@@H:15]4[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]4)=[CH:4][CH:3]=3)=[CH:43][C:39]=2[CH:40]=[CH:41]1

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 27951905-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuranHCID 673758331,1-dimethylethyl (3S)-3-{[4-(4-bromophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-1-pyrrolidinecarboxylate

生成物 1

HCID 67376548tert-butyl (3S)-3-({4-[4-(1-benzofuran-5-yl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)pyrrolidine-1-carboxylate収率 96%

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

In a sealed pressure tube, a mixture of 1,1-dimethylethyl (3S)-3-{[4-(4-bromophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-1-pyrrolidinecarboxylate (2.5 g, 5.91 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (1.514 g, 6.20 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.241 g, 0.295 mmol), and sodium bicarbonate (1.488 g, 17.72 mmol) in 1,4-dioxane (30 mL) and water (15 mL) was stirred at 100° C. for 24 h. The reaction was cooled to room temperature. The reaction was diluted with ethyl acetate (300 mL) and water (100 mL), and the layers were separated. The aqueous layer was acidified to pH˜6 using a 1N aq HCl solution and then extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by silica gel chromatography (Analogix IF280, SF40-115g, Solvent A: ethyl acetate; Solvent B: 10% methanol/dichloromethane; Gradient: 100% A for 10 min, then 0-50% B/A over 20 min) provided the title compound as a tan solid (2.6 g, 96%). MS(ES)+ m/e 461.4 [M+H]+.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. customthe layers were separated
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by silica gel chromatography (Analogix IF280, SF40-115g, Solvent A
  7. waitGradient: 100% A for 10 min

出典と根拠

ORDレコード
ord-805c79092eb846d08cc86873d82ed16c
出典データセット
uspto-grants-2016_05
特許番号
US09340529B2

反応ノート

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