Isobutylene oxide → 1''-(2-Hydroxy-2-methyl-propyl)-5-(4-methylsulfonyl-phenyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

HRID 2406335Notes

Reaction equation

HRID 2406335 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[CH2:27][C:18]4([CH2:26][C:20]5([CH2:25][CH2:24][NH:23][CH2:22][CH2:21]5)[CH2:19]4)[O:17][C:14]3=[CH:15][N:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C([O-])([O-])=O.[K+].[K+].[CH3:34][C:35]1([O:38][CH2:37]1)[CH3:36]>CO>[OH:38][C:35]([CH3:37])([CH3:36])[CH2:34][N:23]1[CH2:22][CH2:21][C:20]2([CH2:26][C:18]3([O:17][C:14]4=[CH:15][N:16]=[C:11]([C:8]5[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=5)[CH:12]=[C:13]4[CH2:27]3)[CH2:19]2)[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 11208Isobutylene oxideHCID 11430Potassium CarbonateHCID 867012015-(4-Methylsulfonyl-phenyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Product 1

HCID 867012021''-(2-Hydroxy-2-methyl-propyl)-5-(4-methylsulfonyl-phenyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 5-(4-methylsulfonyl-phenyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1′-cyclobutane-3′,4″-piperidine] (HCl salt; 50 mg) and K2CO3 (17 mg) in methanol (4 mL) is stirred at room temperature for 15 min prior to the addition of isobutylene oxide (20 μL). The reaction vessel is sealed and the mixture is stirred at 60° C. overnight. After cooling to room temperature, the mixture is concentrated and the residue is chromatographed on silica gel (cyclohexane/ethyl acetate/methanol 5:4:1→0:9:1) to give the title compound. LC (method 1): tR=0.71 min; Mass spectrum (ESI+): m/z=457 [M+H]+.

Workup

  1. customThe reaction vessel is sealed
  2. stirringthe mixture is stirred at 60° C. overnight
  3. temperatureAfter cooling to room temperature
  4. concentrationthe mixture is concentrated
  5. customthe residue is chromatographed on silica gel (cyclohexane/ethyl acetate/methanol 5:4:1→0:9:1)

Sources & evidence

ORD record
ord-a676e96026e740419e8fdc8e89db3a52
Source dataset
uspto-grants-2014_08
Patent number
US08809361B2

Reaction notes

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