Acetate → 5-(2-Cyano-4-methylsulfanyl-phenyl)-1''-tert-butoxycarbonyl-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

HRID 2406363Notes

Reaction equation

HRID 2406363 reaction equation
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]3[CH2:32][C:16]4([CH2:31][C:18]5([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]5)[CH2:17]4)[O:15][C:12]3=[CH:13][N:14]=2)=[CH:5][CH:4]=1.[C-]#N.[K+].C([O-])(=O)C.[CH3:40][N:41](C)C=O>[Cu](Br)Br.O>[C:40]([C:7]1[CH:8]=[C:3]([S:2][CH3:1])[CH:4]=[CH:5][C:6]=1[C:9]1[CH:10]=[C:11]2[CH2:32][C:16]3([CH2:17][C:18]4([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:20][CH2:19]4)[CH2:31]3)[O:15][C:12]2=[CH:13][N:14]=1)#[N:41]

Participants

7

Reactant 4

HCID 175AcetateHCID 6228DimethylformamideHCID 9032Potassium CyanideHCID 721951175-(4-Methylsulfanyl-phenyl)-1''-tert-butoxycarbonyl-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Product 1

HCID 721951185-(2-Cyano-4-methylsulfanyl-phenyl)-1''-tert-butoxycarbonyl-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)CatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 5-(4-methylsulfanyl-phenyl)-1″-tert-butoxycarbonyl-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1′-cyclobutane-3′,4″-piperidine] (100 mg), potassium cyanide (22 mg), copper(II) bromide (20 mg), palldium(II) acetate (5 mg), and N,N-dimethylformamide (5 mL) is stirred in air at 130° C. overnight. After cooling to room temperature, water is added and the mixture is extracted with ethyl acetate. The combined extract is dried (Na2SO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate) to give the title compound. LC (method 3): tR=1.17 min; Mass spectrum (ESI+): m/z=478 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture is extracted with ethyl acetate
  3. extractionThe combined extract
  4. dry with materialis dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-5c3a8e7f2a364137b46d603bf9e99ee9
Source dataset
uspto-grants-2014_08
Patent number
US08809361B2

Reaction notes

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