Tetrahydrofuran → 5-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-1''-(1-methyl-cyclopropyloxycarbonyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

HRID 2406347Notes

Reaction equation

HRID 2406347 reaction equation
[C:1](=[O:17])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][C:3]1([CH3:6])[CH2:5][CH2:4]1.[CH3:18][S:19]([N:22]1[CH2:27][CH:26]=[C:25]([C:28]2[CH:29]=[C:30]3[CH2:44][C:35]4([CH2:43][C:37]5([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]5)[CH2:36]4)[O:34][C:31]3=[CH:32][N:33]=2)[CH2:24][CH2:23]1)(=[O:21])=[O:20].C(N(CC)CC)C.O1CCCC1>O>[CH3:18][S:19]([N:22]1[CH2:23][CH:24]=[C:25]([C:28]2[CH:29]=[C:30]3[CH2:44][C:35]4([CH2:36][C:37]5([CH2:38][CH2:39][N:40]([C:1]([O:2][C:3]6([CH3:6])[CH2:4][CH2:5]6)=[O:17])[CH2:41][CH2:42]5)[CH2:43]4)[O:34][C:31]3=[CH:32][N:33]=2)[CH2:26][CH2:27]1)(=[O:21])=[O:20]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 579301151-Methylcyclopropyl 4-nitrophenyl carbonateHCID 867012045-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Product 1

HCID 867012085-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-1''-(1-methyl-cyclopropyloxycarbonyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

1-Methylcyclopropyl 4-nitro-phenyl carbonate (58 mg) is added to a mixture of 5-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1′-cyclobutane-3′,4″-piperidine] (HCl salt; 66 mg), triethylamine (65 μL), and tetrahydrofuran (5 mL) at room temperature. The solution is stirred at 60° C. overnight. Water is added and the resulting mixture is extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 4:1→1:4) to give the title compound. LC (method 1): tR=1.02 min; Mass spectrum (ESI+): m/z=488 [M+H]+.

Workup

  1. extractionthe resulting mixture is extracted with ethyl acetate
  2. dry with materialThe combined extracts are dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 4:1→1:4)

Sources & evidence

ORD record
ord-8d9c7ca38eda47afbd1c020fb73ae731
Source dataset
uspto-grants-2014_08
Patent number
US08809361B2

Reaction notes

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