Acetic Acid → Methyl 4-(1-methylpiperidin-4-YL)benzoate

HRID 16805Notes

Reaction equation

C=O.[C:3](O)(=O)C.[Cl-].[NH2+:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1.C([BH3-])#N.[Na+]>C1COCC1.O>[CH3:3][N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1

Participants

Conditions

Temperature: 60 °C

Procedure

Water (0.4 mL), paraformaldehyde (0.742 g, 24.71 mmol) and acetic acid (1.415 mL, 24.71 mmol) were added to a stirred suspension of methyl 4-piperidin-1-ium-4-ylbenzoate chloride (1.58 g, 6.18 mmol) in THF (40 mL) under nitrogen. Sodium cyanoborohydride (0.582 g, 9.27 mmol) was added portion wise over a period of 10 mins. The resulting mixture was stirred at 60° C. for 18 h. The reaction mixture was evaporated to dryness and mixed with water (30 mL) and 1M HCl (10 mL). The solution was washed with ethyl acetate (2×25 mL), basified with solid potassium carbonate and extracted ethyl acetate (2×25 mL). The organic layer was washed with saturated brine and dried over MgSO4, filtered and evaporated to afford pure methyl 4-(1-methylpiperidin-4-yl)benzoate (0.784 g, 54.4%) as a colourless oil which solidified on standing.

Workup

customThe reaction mixture was evaporated to dryness
additionmixed with water (30 mL) and 1M HCl (10 mL)
washThe solution was washed with ethyl acetate (2×25 mL)
extractionextracted ethyl acetate (2×25 mL)
washThe organic layer was washed with saturated brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-de12d9ffa5294cfa9a229c3e98a08547
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737149B2

Reaction notes

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