Ammonia → 2-Methyl-N-[3-(1-((3S)-3-Phenyl-3-[4-(Trifluoromethyl)Phenoxy]Propyl)-4-Piperidinyl)Phenyl]Propanamide

HRID 1832178Notes

Reaction equation

HRID 1832178 reaction equation
[OH:1][C@@H:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1.[F:29][C:30]([F:39])([F:38])[C:31]1[CH:36]=[CH:35][C:34](O)=[CH:33][CH:32]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.N>C1COCC1.C(Cl)(Cl)Cl>[CH3:20][CH:19]([CH3:21])[C:18]([NH:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([CH:8]2[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][C@@H:2]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[O:1][C:34]3[CH:35]=[CH:36][C:31]([C:30]([F:39])([F:38])[F:29])=[CH:32][CH:33]=3)[CH2:6][CH2:7]2)[CH:12]=1)=[O:22]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 11776TriphenylphosphineHCID 678744-(Trifluoromethyl)phenolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10199805N-(3-(1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide

Product 1

HCID 600787162-Methyl-N-[3-(1-((3S)-3-Phenyl-3-[4-(Trifluoromethyl)Phenoxy]Propyl)-4-Piperidinyl)Phenyl]PropanamideYield 38.9%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-(3-{1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide (9.53 mg, 0.0250 mmol), 4-trifluoromethylphenol (8.100 mg, 0.050 mmol), triphenylphosphine (9.8 mg, 0.0375 mmol) and diethyl azodicarboxylate (5.22 mg, 0.0300 mmol) in THF (1.0 mL) was stirred at room temperature for 3 days. Chromatography using silica preparative TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] gave the desired product (5.10 mg, 38.9% yield) as a thick oil: 1H NMR δ 8.06 (s, 1H), 7.49 (s, 1H), 7.44 (apparent d, 2H, J=0.6 Hz), 7.38–7.30 (m, 4H), 7.30–7.20 (m, 3H), 6.96 (apparent d, 1H, J=7.6 Hz), 6.91 (apparent d, 2H, J=8.6 Hz), 5.34 (m, 1H), 3.19 (m, 2H), 2.72 (m, 2H) 2.53 (m, 2H), 2.40–1.80 (m, 8H), 1.25 (d, 6H, J=6.8 Hz); ESMS m/e: 525.4 (M+H)+.

Sources & evidence

ORD record
ord-5f0a297e87ef4fe5bcdabfc2674530ca
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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