Hydrochloric Acid → Biphenyl-2-ylcarbamic acid 1-[2-(4-formyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester

HRID 2246519Notes

Reaction equation

[O:1]1CCO[CH:2]1[C:6]1[C:11]([CH3:12])=[CH:10][C:9]([NH:13][C:14]([CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][CH:21]([O:24][C:25](=[O:39])[NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:20][CH2:19]2)=[O:15])=[C:8]([CH3:40])[CH:7]=1.C(#N)C.Cl.[OH-].[Na+]>C(OCC)(=O)C>[CH:2]([C:6]1[C:11]([CH3:12])=[CH:10][C:9]([NH:13][C:14]([CH2:16][CH2:17][N:18]2[CH2:19][CH2:20][CH:21]([O:24][C:25](=[O:39])[NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:22][CH2:23]2)=[O:15])=[C:8]([CH3:40])[CH:7]=1)=[O:1]

Participants

Conditions

Temperature: 30 °C

Procedure

To a 500 mL round-bottom flask was added biphenyl-2-ylcarbamic acid 1-[2-(4-[1,3]dioxolan-2-yl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (15 g, 27.6 mmol) and acetonitrile (150 mL) to form a slurry. Aqueous 2 M hydrochloric acid (75 mL) was added and the resulting mixture was stirred at 30° C. for 1 hour. The mixture was then cooled to room temperature and ethyl acetate (150 mL) was added. Aqueous 2 M sodium hydroxide (75 mL) was added, the pH was checked and then additional 2 M sodium hydroxide was added until the pH of the solution was in the range of 9 to 10. The layers were separated and the organic layer was washed with diluted brine (75 mL; 1:1 brine/water), dried over anhydrous sodium sulfate and the solvent removed on a rotary evaporator to give biphenyl-2-ylcarbamic acid 1-[2-(4-formyl-2,5-dimethylphenyl-carbamoyl)ethyl]piperidin-4-yl ester (12.5 g, about 98% purity). If desired, the purity of this intermediate can be increased by forming a slurry with ethanol (3 volumes of ethanol), heating the slurry to 80° C., and then cooling slowly to room temperature and isolating by filtration.

Workup

customto form a slurry
temperatureThe mixture was then cooled to room temperature
customThe layers were separated
washthe organic layer was washed with diluted brine (75 mL; 1:1 brine/water)
dry with materialdried over anhydrous sodium sulfate
customthe solvent removed on a rotary evaporator

Sources & evidence

ORD record: ord-fe82148e8aef47aab6659e666da4d703
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07687521B2

Reaction notes

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