Ammonia → N-(3-{1-[3,5-Bis(Trifluoromethyl)Benzyl]-4-Piperidinyl}Phenyl)-2-Methylpropanamide

HRID 1832172Notes

Reaction equation

HRID 1832172 reaction equation
[CH3:1][CH:2]([CH3:18])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:7]=1)=[O:4].[F:19][C:20]([F:34])([F:33])[C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:24]Br.C(N(C(C)C)CC)(C)C.N>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)(Cl)Cl.O1CCOCC1>[F:19][C:20]([F:33])([F:34])[C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=1)[CH2:24][N:15]1[CH2:16][CH2:17][CH:12]([C:8]2[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:18])[CH3:1])[CH:11]=[CH:10][CH:9]=2)[CH2:13][CH2:14]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamide

Product 1

HCID 22048609N-(3-{1-[3,5-Bis(Trifluoromethyl)Benzyl]-4-Piperidinyl}Phenyl)-2-MethylpropanamideYield 25.8%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (28.3 mg, 0.100 mmol), 3,5-bis(trifluoromethyl)benzyl bromide (38.4 mg, 0.125 mmol), diisopropylethylamine (0.50 mL), catalytic amount of tetrabutylammonium iodide and dioxane (2.0 mL). Chromatography using silica preparative TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] gave the desired product (12.2 mg, 25.8% yield) as a thick oil: 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 2H), 7.77 (s, 1H), 7.53 (s, 1H), 7.30–7.21 (m, 2H), 7.16 (s, 1H), 6.98 (apparent d, 1H, J=7.6 Hz), 3.62 (s, 2H), 2.94 (d, 2H, J=9.4 Hz), 2.51 (apparent sept, partially hidden, 2H, J=6.6 Hz), 2.14 (m, 2H), 1.82 (m, 4H), 1.25 (d, 6H, J=6.6 Hz); ESMS m/e: 473.2 (M+H)+.

Sources & evidence

ORD record
ord-b2eccae06d8c4ef0a3e9ec0526c2f4bb
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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