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

HRID 2196546Notes

Reaction equation

HRID 2196546 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-d7e6aa9f51454896802b6edd704bb1d8
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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