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

HRID 1633540Notes

Reaction equation

HRID 1633540 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][CH2:8][C:7]([C:19]3[CH:24]=[CH:23][C:22](OS(C(F)(F)F)(=O)=O)=[CH:21][CH:20]=3)([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=3)[CH2:6]2)[CH2:3][CH2:2]1.[S:33]1[CH:37]=[CH:36][CH:35]=[C:34]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>[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][CH2:8][C:7]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=3)([C:19]3[CH:24]=[CH:23][C:22]([C:34]4[S:33][CH:37]=[CH:36][CH:35]=4)=[CH:21][CH:20]=3)[CH2:6]2)[CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 54380713Trifluoro-methanesulfonic acid 4-[1-cyclopropylmethyl-3-(3-methoxy-phenyl)-piperidin-3-yl]-phenyl ester

Product 1

HCID 185071541-Cyclopropylmethyl-3-(3-methoxy-phenyl)-3-(4-thiophen-2-yl-phenyl)-piperidineYield 99.1%

Reagents, catalysts & solvents 4

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

Procedure

To a solution of trifluoro-methanesulfonic acid 4-[1-cyclopropylmethyl-3-(3-methoxy-phenyl)-piperidin-3-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 of 1-cyclopropylmethyl-3-(3-methoxy-phenyl)-3-(4-thiophen-2-yl-phenyl)-piperidine. 1HNMR (400 MHz, CDCl3) δ 749 (d, 2H), 7.35 (d, 2H), 7.22-7.06 (comp, 3H), 7.05-7.00 (m, 1H), 6.96 (s, 1H), 6.89 (d, 1H), 6.70-6.67 (m, 1H), 3.76 (m, 3H), 3.17-2.82 (comp, 2H), 2.61-2.39 (comp, 2H), 2.27-2.18 (comp, 4H), 1.62-1.39 (comp, 3H), 0.60-0.45 (comp, 2H), 0.18-0.11 (comp, 2H); MS (M+1) 404.2.

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-462a92424cfd4393a454d867e7281509
Source dataset
uspto-grants-2003_01
Patent number
US06503905B1

Reaction notes

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