Potassium Phosphate, Tribasic → 1-{[7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol

HRID 473871

反応式

HRID 473871 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:19][CH2:18][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)([OH:20])[CH2:16][CH2:15]3)=[O:13])[CH2:7][C:6]=2[CH:31]=1.[N+:32]([C:35]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[CH:38][C:36]=1[NH2:37])([O-:34])=[O:33].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[NH2:37][C:36]1[CH:38]=[CH:39][C:40]([C:2]2[CH:3]=[CH:4][C:5]3[O:11][CH2:10][CH2:9][N:8]([C:12]([N:14]4[CH2:19][CH2:18][C:17]([C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=5)([OH:20])[CH2:16][CH2:15]4)=[O:13])[CH2:7][C:6]=3[CH:31]=2)=[CH:41][C:35]=1[N+:32]([O-:34])=[O:33]

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 162179142-Nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 696722991-[(7-bromo-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl)carbonyl]-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol

生成物 1

HCID 866720271-{[7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol収率 26%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To a solution of 1-[(7-bromo-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl)carbonyl]-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol (0.688 g, 1.38 mmol) and 2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.365 g, 1.38 mmol) in dioxane (24 mL) and water (3.00 ml) was added tribasic potassium phosphate (0.413 g, 1.79 mmol). The solution was sparged with N2(g) for ten minutes before the addition of dichloro[1,1-bis-(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.023 g, 10 mol %). The resulting suspension was heated at 90° C. for 2 hours in a sealed tube vessel. On cooling to room temperature the mixture was diluted with ethyl acetate (50 mL), washed with water (50 mL) and then dried over anhydrous sodium sulfate. Filtration and concentration afforded a crude orange oil that was purified by silica gel chromatography (7:3 hexanes/ethyl acetate) to provide 1-{[7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol (0.200 g, 26% yield) as an orange oil. MS (EI) for C28H27F3N4O5: 557 (MH+).

後処理

  1. customThe solution was sparged with N2(g) for ten minutes before the addition of dichloro[1,1-bis-(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.023 g, 10 mol %)
  2. temperatureOn cooling to room temperature the mixture
  3. additionwas diluted with ethyl acetate (50 mL)
  4. washwashed with water (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationFiltration and concentration
  7. customafforded a crude orange oil that
  8. customwas purified by silica gel chromatography (7:3 hexanes/ethyl acetate)

出典と根拠

ORDレコード
ord-bdef0e6c99d74db49ff204df15b28f9f
出典データセット
uspto-grants-2014_01
特許番号
US08637499B2

関連ノート

読み込み中…