Trifluoroacetic acid → N-(4-fluorobenzyl)-N-(3-fluorophenyl)-4-piperidinamine

HRID 1724667Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[N:5]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:6]1[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]1.C(O)(C(F)(F)F)=O>ClCCl>[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:5]([C:4]2[CH:27]=[CH:28][CH:29]=[C:2]([F:1])[CH:3]=2)[CH:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]2)=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Tert-butyl 4-[3-fluoro(4-fluorobenzyl)anilino]-1-piperidinecarboxylate 8 (25.5 g) was dissolved in dichloromethane and the solution was cooled to 0° C. TFA (30 ml) was added to the solution and the reaction mixture was stirred at room temperature. After 1 h 30, TFA (20 ml) was added and the reaction mixture was stirred for a further 30 minutes. The solvent was removed under vacuum and the residue was taken up in dichloromethane and water. The aqueous phase was alkalized by addition of NaOH and washed with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated. The crude was purified by chromatography (eluant: CH2Cl2/MeOH/NH4OH 95/5/0.5) to give N-(4-fluorobenzyl)-N-(3-fluorophenyl)-4-piperidinamine (18.4 g) as a free base.

Workup

stirringthe reaction mixture was stirred for a further 30 minutes
customThe solvent was removed under vacuum
additionThe aqueous phase was alkalized by addition of NaOH
washwashed with dichloromethane
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated
customThe crude was purified by chromatography (eluant: CH2Cl2/MeOH/NH4OH 95/5/0.5)

Sources & evidence

ORD record: ord-dc4933c8a828413c9fe717a3d976430e
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07488741B2

Reaction notes

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