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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 1255181
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Reaktionsgleichung

Reaktionsgleichung von HRID 1255181
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
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Komponenten

4

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-d7ff5e0a5fc14455958ff04ed3e57043
Quelldatensatz
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08455638B2

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