Methyl iodide → 4-(4-Methoxypiperidin-1-yl)benzoic acid

HRID 1264324Notes

Reaction equation

HRID 1264324 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH3:17]I.[H-].[Na+]>C1COCC1.CS(C)=O.[Cl-].[Na+].O>[CH3:17][O:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 186175914-(4-Hydroxy-1-piperidinyl)benzoic acid

Product 1

HCID 186174664-(4-Methoxypiperidin-1-yl)benzoic acidYield 33.1%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

170 mg (0.77 mmol) of 4-(4-hydroxy-piperidin-1-yl)-benzoic acid (reference example 113d) were dissolved in 3 ml of THF and 3 ml of DMSO, 120 mg (1.1 equiv) of methyl iodide and 68 mg (1.69 mmol) of NaH were added and stirred 16 h at room temperature. The mixture was poured into brine and extracted with DCM (3×) aqueous phase acidified with HCl to pH 1 and extracted again with DCM (3×). The combined organic extracts were washed with brine, dried with Na2SO4, filtered and evaporated. TLC (DCM/MeOH 10%) showed a mixture of the starting material (Rf˜0.5) and a new product with Rf˜0.6. The two were separated by chromatography on silica with DCM/MeOH (0-10%) as a mobile phase to give 60 mg of the title compound. 1H NMR (CDCl3): d 7.95 (d, 2H), 6.87 (d, 2H), 3.68 (m, 2H), 3.63 (m, 1H), 3.38 (s, 3H), 3.14 (m, 2H), 1.98 (m, 2H), 1.68 (m, 2H). MS (ion spray) m/z 236 (M+H)+.

Workup

  1. extractionextracted with DCM (3×) aqueous phase
  2. extractionextracted again with DCM (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. additiona mixture of the starting material (Rf˜0.5)
  8. customThe two were separated by chromatography on silica with DCM/MeOH (0-10%) as a mobile phase

Sources & evidence

ORD record
ord-9d6e26f5e2ff4b7885bd96967fd6631a
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

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