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

HRID 1911361Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

Water (0.2 mL), paraformaldehyde (0.470 g, 15.64 mmol) and acetic acid (0.895 mL, 15.64 mmol) were added to a stirred suspension of 4-(4-(methoxycarbonyl)phenyl)piperidinium chloride (1 g, 3.91 mmol) in THF (20 mL) under nitrogen. Sodium cyanoborohydride (0.369 g, 5.87 mmol) was added portionwise over a period of 10 mins. The resulting mixture was stirred at 60° C. for 19 h. The reaction mixture was evaporated to dryness and mixed with water (20 mL) and 1M HCl (5 mL). The solution was washed with EtOAc (2×15 mL), basified with K2CO3 and extracted with EtOAc (2×15 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 (0.459 g, 50.4%) as a colourless oil which crystallised on standing.

Workup

customThe reaction mixture was evaporated to dryness
additionmixed with water (20 mL) and 1M HCl (5 mL)
washThe solution was washed with EtOAc (2×15 mL)
extractionextracted with EtOAc (2×15 mL)
washThe organic layer was washed with saturated brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-885119e0ed114867ae9fd2e786468d1a
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604022B2

Reaction notes

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