Hydrochloric Acid → Benzyl 3-hydroxy-4-(4-hydroxyphenyl)piperidinecarboxylate

HRID 1176512Notes

Reaction equation

[OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])(C)C)=[O:16])[CH2:3]1.CO.Cl>C(Cl)(Cl)Cl>[OH:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][CH2:18][C:21]2[CH:3]=[CH:2][CH:7]=[CH:6][CH:5]=2)=[O:16])[CH2:3]1

Participants

Conditions

Temperature: 60 °C

Procedure

The mixture of 6.0 g of tert-butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate, 120 ml of methanol, 40 ml of chloroform and 20 ml of 2M HCl is stirred at 60° C. over 20 hours. The reaction mixture is cooled and the organic solvent is evaporated off. The resulting aqueous solution is admixed with stirring with 80 ml of saturated sodium hydrogencarbonate solution and 80 ml of ethyl acetate. The biphasic mixture is cooled to 0° C. and admixed slowly with 3.30 ml of benzyl chloroformate and stirred over a further 2 hours. The reaction mixture is extracted with ethyl acetate-tetrahydrofuran. The organic phases are concentrated by evaporation and the title compound is obtained as a white solid from the residue by means of crystallization (ethyl acetate-heptane). Rt=5.72.

Workup

temperatureThe reaction mixture is cooled
customthe organic solvent is evaporated off
stirringwith stirring with 80 ml of saturated sodium hydrogencarbonate solution and 80 ml of ethyl acetate
temperatureThe biphasic mixture is cooled to 0° C.
stirringstirred over a further 2 hours
extractionThe reaction mixture is extracted with ethyl acetate-tetrahydrofuran
concentrationThe organic phases are concentrated by evaporation

Sources & evidence

ORD record: ord-c975cbf5905b419a9d8f1c4883b0fca1
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842688B2

Reaction notes

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