Sodium Hydroxide → {3-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-5-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 2285178Notes

Reaction equation

HRID 2285178 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:12]=[N:13][N:14]([CH2:16][CH2:17][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[CH:15]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl[C:28]([O:30][CH2:31][C:32]([Cl:35])([Cl:34])[Cl:33])=[O:29]>O.CCOC(C)=O>[Cl:33][C:32]([Cl:35])([Cl:34])[CH2:31][O:30][C:28](=[O:29])[NH:10][C:8]1[N:7]([C:11]2[CH:12]=[N:13][N:14]([CH2:16][CH2:17][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[CH:15]=2)[N:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:9]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 866871743-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4]bipyrazolyl-5-ylamine

Product 1

HCID 86687175{3-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-5-yl}-carbamic acid 2,2,2-trichloro-ethyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of Intermediate 108a (1.29 g, 3.87 mmol) in water (5 mL) and EtOAc (13 mL) was added NaOH (310 mg, 7.74 mmol). After 10 min stirring, 2,2,2-trichloroethyl chloroformate (640 μL, 4.65 mmol) was added and the reaction mixture was stirred at RT for 1 h. The aqueous layer was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-75% EtOAc in cyclohexane, to afford the title compound (1.24 g, 63%). LCMS (Method 4): Rt 3.92 min, m/z 508, 510 [MH+].

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 h
  2. extractionThe aqueous layer was extracted with EtOAc (×3)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-c4e1c550c9ed41c0a79c3ff44862d304
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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