Sodium Iodide → 5-(4-Methylsulfonyl-phenyl)-1''-[(1-trifluoromethyl-cyclopropyl)-methyl]-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

HRID 2406341Notes

Reaction equation

HRID 2406341 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1([CH2:6]OS(C)(=O)=O)[CH2:5][CH2:4]1.[I-].[Na+].[CH3:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[C:28]3[CH2:42][C:33]4([CH2:41][C:35]5([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]5)[CH2:34]4)[O:32][C:29]3=[CH:30][N:31]=2)=[CH:22][CH:21]=1)(=[O:19])=[O:18].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.O>[CH3:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[C:28]3[CH2:42][C:33]4([CH2:41][C:35]5([CH2:36][CH2:37][N:38]([CH2:6][C:3]6([C:2]([F:1])([F:12])[F:13])[CH2:4][CH2:5]6)[CH2:39][CH2:40]5)[CH2:34]4)[O:32][C:29]3=[CH:30][N:31]=2)=[CH:22][CH:21]=1)(=[O:19])=[O:18]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 86649942(1-(Trifluoromethyl)cyclopropyl)methyl methanesulfonateHCID 867012015-(4-Methylsulfonyl-phenyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Product 1

HCID 721948535-(4-Methylsulfonyl-phenyl)-1''-[(1-trifluoromethyl-cyclopropyl)-methyl]-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of methanesulfonic acid (1-trifluoromethyl-cyclopropyl)methyl ester (45 mg) and sodium iodide (34 mg) in N,N-dimethylformamide (2 mL) is stirred at room temperature for 4 h. 5-(4-Methylsulfonyl-phenyl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1′-cyclobutane-3′,4″-piperidine] (HCl salt; 50 mg) and K2CO3 (35 mg) are added and the resulting mixture is heated to 60° C. After stirring the mixture at 60° C. for 4 h, water is added and the mixture is extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and concentrated. The residue is triturated with methanol to give the title compound. LC (method 1): tR=0.82 min; Mass spectrum (ESI+): m/z=507 [M+H]+.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. dry with materialThe combined extracts are dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue is triturated with methanol

Sources & evidence

ORD record
ord-bc3af0339b074e86b8ffb4d69282f849
Source dataset
uspto-grants-2014_08
Patent number
US08809361B2

Reaction notes

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