Potassium Carbonate → Methyl 4-{[4-(2-{[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}ethyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylate

HRID 2410331Notes

Reaction equation

HRID 2410331 reaction equation
[OH:1][C:2]1[C:7]2[C:8]([O:11][CH2:12][CH2:13][CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4([C:27]([O:29][CH3:30])=[O:28])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH2:16][CH2:15]3)=[N:9][O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:43][C:44]([F:47])([F:46])[F:45])(=O)=O>CN(C)C=O>[F:45][C:44]([F:47])([F:46])[CH2:43][O:1][C:2]1[C:7]2[C:8]([O:11][CH2:12][CH2:13][CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4([C:27]([O:29][CH3:30])=[O:28])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH2:16][CH2:15]3)=[N:9][O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 136367381Methyl 4-[(4-{2-[(4-hydroxy-1,2-benzisoxazol-3-yl)oxy]ethyl}piperidin-1-yl)methyl]tetrahydro-2H-pyran-4-carboxylate

Product 1

HCID 69317424Methyl 4-{[4-(2-{[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}ethyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred mixture of methyl 4-[(4-{2-[(4-hydroxy-1,2-benzisoxazol-3-yl)oxy]ethyl}piperidin-1-yl)-methyl]tetrahydro-2H-pyran-4-carboxylate (0.63 g, 1.5 mmol, EXAMPLE 7, step 6) and potassium carbonate in N,N-dimethylformamide (3.0 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.26 mL, 1.8 mmol) at 70° C. After being stirred at 70° C. for 3 h, the mixture was cooled to room temperature. The mixture was extracted with ethyl acetate (50 mL×2) and washed with water and brine. The extracts were combined and dried over magnesium sulfate and concentrated in vacuo to give a yellow oil. The residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 2:1) to give 0.69 g (92%) of the title compound as a colorless viscous oil.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (50 mL×2)
  3. washwashed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a yellow oil
  7. customThe residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-0795553e63aa4eddab9bdfdd24d72899
Source dataset
uspto-grants-2014_08
Patent number
US08816090B2

Reaction notes

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