Sodium Carbonate → 1-Benzyl-4-(3-methoxy-phenyl)-4-(4-thiophen-2-yl-phenyl)-piperidine

HRID 2085459Notes

Reaction equation

HRID 2085459 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:22]2[CH:27]=[CH:26][C:25](OS(C(F)(F)F)(=O)=O)=[CH:24][CH:23]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:36]1[CH:40]=[CH:39][CH:38]=[C:37]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].P>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)([C:22]2[CH:27]=[CH:26][C:25]([C:37]3[S:36][CH:40]=[CH:39][CH:38]=3)=[CH:24][CH:23]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 54436264Trifluoro-methanesulfonic acid 4-[1-benzyl-4-(3-methoxy-phenyl)piperidin-4-yl]-phenyl ester

Product 1

HCID 227299341-Benzyl-4-(3-methoxy-phenyl)-4-(4-thiophen-2-yl-phenyl)-piperidineYield 92%

Reagents, catalysts & solvents 4

HCID 2241076578452-78-5CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of trifluoro-methanesulfonic acid 4-[1-benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-phenyl ester (0.1 g, 0.2 mmol) in ethanol (4.5 mL) and water (0.5 mL) was added 2-thiophene boronic acid (0.052 g, 0.5 mmol) and sodium carbonate (0.037 g, 0.29 mmol) and tetrakis tripheny;phosphine palladium (0.02 g, 0.18 mmol). The reaction mixture was heated to reflux for 2 hours. The mixture was then filtered and the filtrate was concentrated under vacuum. The residue was purified by flash chromatography with hexanes/EtOAc (3:1) to afford 0.08 g (92% yield) of 1-Benzyl-4-(3-methoxy-phenyl)-4-(4-thiophen-2-yl-phenyl)-piperidine. 1HNMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.33-7.18 (comp, 10H), 7.07-7.00 (m, 1H), 6.89-6.63 (comp, 2H), 6.69 (d, 1H), 3.76 (s, 3H), 3.42 (s, 2H), 2.61-2.39 (comp, 8H); MS (M+1) 440.2.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. filtrationThe mixture was then filtered
  4. concentrationthe filtrate was concentrated under vacuum
  5. customThe residue was purified by flash chromatography with hexanes/EtOAc (3:1)

Sources & evidence

ORD record
ord-29654cd2d71d4ef59dd67d8ce324afa2
Source dataset
uspto-grants-2004_04
Patent number
US06720336B2

Reaction notes

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