Triethylamine → 1-[4-Methyl-3-(tetrahydro-pyran-2-yloxymethyl)-pyridin-2-ylmethyl]-3-trifluoromethyl-1H-pyridin-2-one

HRID 1959605Notes

Reaction equation

HRID 1959605 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8]O)[C:3]=1[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.CCN(CC)CC.CS(Cl)(=O)=O.[F:30][C:31]([F:40])([F:39])[C:32]1[C:33]([OH:38])=[N:34][CH:35]=[CH:36][CH:37]=1>C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][N:34]2[CH:35]=[CH:36][CH:37]=[C:32]([C:31]([F:39])([F:40])[F:30])[C:33]2=[O:38])[C:3]=1[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 36784112(1H)-Pyridinone, 3-(trifluoromethyl)-HCID 44191034[4-Methyl-3-(tetrahydro-pyran-2-yloxymethyl)-pyridin-2-yl]-methanol

Product 1

HCID 441901701-[4-Methyl-3-(tetrahydro-pyran-2-yloxymethyl)-pyridin-2-ylmethyl]-3-trifluoromethyl-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

[4-Methyl-3-(tetrahydro-pyran-2-yloxymethyl)-pyridin-2-yl]-methanol (138 mg. 0.58 mmol) was dissolved in DCM (5 mL) and cooled to 0° C. NEt3 (324 μL. 2.33 mmol) and methanesulfonyl chloride (90 μL. 1.16 mmol) were added and the reaction mixture was stirred for 1 h at 0° C. After removal of the solvents in vacuo the residue was dissolved in DMF (10 mL) and CsCO3 (570 mg. 1.75 mmol) and 3-trifluoromethyl-pyridin-2-ol (142 mg. 0.87 mmol) were added. After stirring for 2 h at RT the solvent was removed in vacuo and the residue was partioned between water (20 mL) and DCM (20 mL) extracted with DCM (3×20 mL) and the combined organic fractions were dried over Na2SO4 filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EtOAc 2:1→1:1) to give the title compound. MS (m/z): 382.9 [M+H+].

Workup

  1. customAfter removal of the solvents in vacuo the residue
  2. dissolutionwas dissolved in DMF (10 mL)
  3. stirringAfter stirring for 2 h at RT the solvent
  4. customwas removed in vacuo
  5. extractionextracted with DCM (3×20 mL)
  6. dry with materialthe combined organic fractions were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel (elution with hexane/EtOAc 2:1→1:1)

Sources & evidence

ORD record
ord-c12b4d19b60d4ec19be8b9d9911f908d
Source dataset
uspto-grants-2013_04
Patent number
US08410134B2

Reaction notes

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