Ethyl 1-[6-(2-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate → Ethyl 1-[6-(2-{[4-(4-oxocyclohexyl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1255181Notes

Reaction equation

HRID 1255181 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:44]=[CH:43][C:14]([CH2:15][O:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[C:23]4[N:28]=[C:27]([N:29]5[C:33]([C:34]([F:37])([F:36])[F:35])=[C:32]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:31]=[N:30]5)[CH:26]=[CH:25][CH:24]=4)=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[O:4]CC1>C(O)(=O)C.O>[O:4]=[C:5]1[CH2:6][CH2:7][CH:8]([C:11]2[CH:12]=[CH:13][C:14]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:28]=[C:27]([N:29]4[C:33]([C:34]([F:36])([F:37])[F:35])=[C:32]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:31]=[N:30]4)[CH:26]=[CH:25][CH:24]=3)=[CH:43][CH:44]=2)[CH2:9][CH2:10]1

Participants

4

Reactant 1

HCID 67159196Ethyl 1-[6-(2-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 67159542Ethyl 1-[6-(2-{[4-(4-oxocyclohexyl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A solution of the title compound from Example 10 Step D (300 mg, 0.49 mmol) in acetic acid (1.8 mL) and water (0.6 mL) was stirred at 80° C. After 2 h, the mixture was allowed to cool to ambient temperature, then was concentrated in vacuo. The resulting oil was diluted with ether, then was washed successively with water, saturated aqueous sodium bicarbonate, water, and brine. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 20% EtOAc in hexanes, then 20 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 564.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.96 (dd, J=8.0, 1.5 Hz, 1H), 7.87 (t, J=8.0 Hz, 1H), 7.54 (d, J=7.5 Hz, 1H), 7.40-7.36 (m, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.12 (t, J=7.5 Hz, 1H), 7.07 (d, J=7.5 Hz, 1H), 5.14 (s, 2H), 4.38 (q, J=7.0 Hz, 2H), 3.04 (dddd, J=12.0, 12.0, 3.5, 3.5 Hz, 1H), 2.54-2.50 (m, 4H), 2.25-2.21 (m, 2H), 1.99-1.91 (m, 2H), 1.39 (t, J=7.0 Hz, 3H).

Workup

  1. concentrationwas concentrated in vacuo
  2. additionThe resulting oil was diluted with ether
  3. washwas washed successively with water, saturated aqueous sodium bicarbonate, water, and brine
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography on silica gel (0 to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-d7ff5e0a5fc14455958ff04ed3e57043
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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