4-(4-Chloro-3-(trifluoromethyl)phenyl)piperidin-4-ol → HCID 11224422, compound

HRID 1670776Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([NH:10][C:11](=[O:15])OCC)=[N:2]1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([OH:29])[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:19][C:18]=1[C:30]([F:33])([F:32])[F:31]>CS(C)=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([NH:10][C:11]([N:26]2[CH2:27][CH2:28][C:23]([C:20]3[CH:21]=[CH:22][C:17]([Cl:16])=[C:18]([C:30]([F:32])([F:31])[F:33])[CH:19]=3)([OH:29])[CH2:24][CH2:25]2)=[O:15])=[N:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

Ethyl 1H-indazol-3-ylcarbamate (synthesized according to the method described in Tetrahedron, 1976, 32(4), 493)(200 mg) and 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidine (ACROS CO., 272 mg) were dissolved in dimethyl sulfoxide (2 ml). Potassium fluoride-alumina (Aldrich Co., 40 wt %, 200 mg) was added to the solution, and the mixture was stirred with heating at 100° C. for 2 hr. After completion of the reaction, the solid was collected by filtration and washed with methanol. The filtrate was concentrated, and 1N aqueous hydrochloric acid was added. The precipitated solid was collected by filtration and vacuum dried. The obtained solid was washed with diethyl ether and dried to give 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxy-1-piperidinecarboxylic acid (1H-indazol-3-yl)amide (280 mg, yield 66%).

Workup

customAfter completion of the reaction
filtrationthe solid was collected by filtration
washwashed with methanol
concentrationThe filtrate was concentrated
addition1N aqueous hydrochloric acid was added
filtrationThe precipitated solid was collected by filtration and vacuum
customdried
washThe obtained solid was washed with diethyl ether
customdried

Sources & evidence

ORD record: ord-0aa40b33e4a547048c8fffc63ebe4f55
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994196B2

Reaction notes

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