Formic Acid → HCID 14032646, compound

HRID 2107438Notes

Reaction equation

[CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.[F:11][C:12]([F:35])([F:34])[C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:20]2)=[CH:15][CH:14]=1.[OH-].[Na+]>CCOCC.O>[CH:1]([N:31]1[CH2:32][CH2:33][CH:28]([C:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:19]([C:16]3[CH:17]=[CH:18][C:13]([C:12]([F:35])([F:34])[F:11])=[CH:14][CH:15]=3)[N:20]=2)[CH2:29][CH2:30]1)=[O:3]

Participants

Conditions

Temperature: 55 °C

Procedure

A stirred mixture of 4-[1-(4-trifluoromethylphenyl)-1H-indazol-3-yl]piperidine-1-carbonitrile of Example 101 (15 g, 0.041 moles) and 25% H2SO4 (100 ml) was refluxed for 20 hours. The mixture was cooled, poured into H2O, and basified with a 25% NaOH solution. The product was extracted (dichloromethane), dried (MgSO4), and concentrated which yielded 13 g (93%) of 1-[4(trifluoromethyl)phenyl]-3-(4-piperidinyl)-1H-indazole as an oil. A mixture of formic acid (1 ml, 0.027 moles) and acetic anhydride (2.4 ml, 0.025 moles) was warmed at 55° C. for 1.5 hours. The solution was cooled to 30° C. and a suspension of the indazole (4.0 g, 0.012 moles) in ether (10 ml) was added. The mixture was stirred at ambient temperature for 3.5 hours and then poured into H2O and basified with a 5% NaOH solution. The product was of an oil. The oil was purified on the high pressure liquid chromatograph (silica gel, 100% ethyl acetate) to yield 3.1 g (72%) of 1-formyl-4-[1-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl]piperidine, m.p. 109°-111° C.

Workup

temperatureThe solution was cooled to 30° C.
additionwas added
customThe oil was purified on the high pressure liquid chromatograph (silica gel, 100% ethyl acetate)

Sources & evidence

ORD record: ord-34f10583e6a94a26ad1ad4aa8d82f621
Source dataset: uspto-grants-1990_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04933460

Reaction notes

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