Sodium Bicarbonate → tert-butyl methyl(2-(4-(5-(2-(trifluoromethoxy)benzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)carbamate

HRID 2196546ノート

反応式

HRID 2196546 の反応式
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][NH2:7].C[Al](C)C.[C:18]([O:22][C:23]([N:25]([CH3:48])[CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][CH:31]([N:34]2[C:38]([C:39](OCC)=[O:40])=[CH:37][C:36]([C:44]([F:47])([F:46])[F:45])=[N:35]2)[CH2:30][CH2:29]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[CH3:48][N:25]([CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][CH:31]([N:34]2[C:38]([C:39](=[O:40])[NH:7][CH2:6][C:5]3[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=3[O:3][C:2]([F:12])([F:13])[F:1])=[CH:37][C:36]([C:44]([F:45])([F:47])[F:46])=[N:35]2)[CH2:30][CH2:29]1)[C:23](=[O:24])[O:22][C:18]([CH3:21])([CH3:19])[CH3:20]

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 2777251(2-(Trifluoromethoxy)phenyl)methanamineHCID 16682925TrimethylaluminumHCID 59843232ethyl 1-(1-(2-(tert-butoxycarbonyl(methyl)amino)ethyl)piperidin-4-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate

生成物 1

HCID 59843247tert-butyl methyl(2-(4-(5-(2-(trifluoromethoxy)benzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)carbamate

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
0 °C

実験手順

To a stirred solution of 2-(Trifluoromethoxy)benzylamine (58.6 mg, 0.307 mmol) in toluene (1.239 mL) at 0° C. was added trimethylaluminium (2M in toluene, 0.557 mL, 1.115 mmol) dropwise. The mixture was stirred for 5 min at 0° C., then a solution of 95 (125 mg, 0.279 mmol) in toluene (0.620 mL) was added dropwise. The mixture was stirred at room temperature for 1 h, then at 55° C. for 1 h, and at 95° C. for 1.5 h till the reaction was complete. Saturated NaHCO3 was added to the reaction mixture followed by extraction with EtOAc. The organic extracts were dried over MgSO4, filtrated and concentrated and the residue was purified via Biotage (5% to 20% MeOH/CH2Cl2; 12M column) to give 99 as yellow oil. LRMS (ESI): calc.593.6; found 594.3 (MH)+.

後処理

  1. stirringThe mixture was stirred at room temperature for 1 h
  2. waitat 55° C. for 1 h
  3. waitat 95° C. for 1.5 h till the reaction was complete
  4. extractionfollowed by extraction with EtOAc
  5. dry with materialThe organic extracts were dried over MgSO4
  6. filtrationfiltrated
  7. concentrationconcentrated
  8. customthe residue was purified via Biotage (5% to 20% MeOH/CH2Cl2; 12M column)

出典と根拠

ORDレコード
ord-d7e6aa9f51454896802b6edd704bb1d8
出典データセット
uspto-grants-2012_12
特許番号
US08338437B2

反応ノート

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