Chloroacetic Acid → Tert-butyl 3-carboxymethoxy-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

HRID 1176268Notes

Reaction equation

[OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:3]1.[H-].[Na+].Cl[CH2:38][C:39]([OH:41])=[O:40].Cl>CN(C)C=O>[C:39]([CH2:38][O:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:3]1)([OH:41])=[O:40]

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 0.953 g of tert-butyl 3-hydroxy-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate in 10 ml of N,N-dimethylformamide is admixed with stirring at room temperature with 0.16 g of sodium hydride dispersions (60%). The reaction mixture is stirred at 60° C. over 10 minutes, admixed with 0.191 g of chloroacetic acid and then stirred at 60° C. over 24 hours. The reaction mixture is admixed with 0.5N HCl and extracted with ethyl acetate (2×). The combined organic phases are washed with brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.20 (95:5 dichloromethane-methanol); Rt=5.18.

Workup

stirringstirred at 60° C. over 24 hours
extractionextracted with ethyl acetate (2×)
washThe combined organic phases are washed with brine
dry with materialdried over sodium sulphate
concentrationconcentrated by evaporation

Sources & evidence

ORD record: ord-f8088d9261bd4b61be6c547036cb852a
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842688B2

Reaction notes

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