Water → 3-(4-Isopropylphenyl)-1',4,6,7-tetramethyl-5-(4-pyridylmethyloxy)spiro[benzofuran-2(3H), 4'-piperidine]

HRID 1743235Notes

Reaction equation

HRID 1743235 reaction equation
[H-].[Na+].[CH:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[C:16]3([CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[O:15][C:14]3[C:23]([CH3:30])=[C:24]([CH3:29])[C:25]([OH:28])=[C:26]([CH3:27])[C:13]2=3)=[CH:8][CH:7]=1)([CH3:5])[CH3:4].Cl.Cl[CH2:33][C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.O>CN(C)C=O>[CH:3]([C:6]1[CH:7]=[CH:8][C:9]([CH:12]2[C:16]3([CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[O:15][C:14]3[C:23]([CH3:30])=[C:24]([CH3:29])[C:25]([O:28][CH2:33][C:34]4[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=4)=[C:26]([CH3:27])[C:13]2=3)=[CH:10][CH:11]=1)([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 745704-(Chloromethyl)pyridinium chlorideHCID 222382593-(4-Isopropylphenyl)-1',4,6,7-tetramethylspiro[benzofuran-2(3H), 4'-piperidine]-5-ol

Product 1

HCID 222382643-(4-Isopropylphenyl)-1',4,6,7-tetramethyl-5-(4-pyridylmethyloxy)spiro[benzofuran-2(3H), 4'-piperidine]Yield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% liquid paraffin dispersion, 187.3 mg, 4.98 mmol) was added to a solution of 3-(4-isopropylphenyl)-1′,4,6,7-tetramethylspiro[benzofuran-2(3H),4′-piperidine]-5-ol (817.7 mg, 2.15 mmol) in N,N-dimethylformamide (30 mL) at 0° C., and the mixture was stirred for 30 minutes at the same temperature. To the reaction mixture was added 4-chloromethylpyridine hydrochloride (364.5 mg, 2.22 mmol) and the mixture was stirred for further 30 minutes at room temperature. The reaction mixture was poured into water, and extracted twice with ethyl acetate. The organic layers were combined, washed with an aqueous saturated sodium hydrogencarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (Chromatorex NH DM1020, Fuji Silysia Chemical LTD) (hexane/ethyl acetate=4/1) to obtain the title compound (575 mg, yield 57%).

Workup

  1. stirringthe mixture was stirred for further 30 minutes at room temperature
  2. extractionextracted twice with ethyl acetate
  3. washwashed with an aqueous saturated sodium hydrogencarbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6968e00de3d0426e8f810e190e06b5fe
Source dataset
uspto-grants-2006_03
Patent number
US07008950B1

Reaction notes

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