Hydrochloric Acid → 4-{3-[4-(3-Hydroxypropyl)-1-piperidinyl]propoxy}benzonitrile monohydrate

HRID 43275Notes

Reaction equation

CS(O[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=1)(=O)=[O:3].[I-].[K+].C(=O)(O)[O-].[Na+].Cl.[NH:26]1[CH2:31][CH2:30][CH:29]([CH2:32][CH2:33][CH2:34][OH:35])[CH2:28][CH2:27]1.Cl>CN(C)C=O.C1(C)C=CC=CC=1.O>[OH2:3].[OH:35][CH2:34][CH2:33][CH2:32][CH:29]1[CH2:30][CH2:31][N:26]([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[CH2:27][CH2:28]1

Participants

Conditions

Temperature: 70 °C

Procedure

Into a solution of 50.0 g of 3-(4-cyanophenoxy)propyl methanesulfonate in 250 mL of N,N-dimethylformamide, 32.5 g of potassium iodide, 32.9 g of sodium bicarbonate and 37.0 g of 3-(4-piperidinyl)-1-propanol hydrochloride were added at room temperature, which was then stirred at 70° C. for 7 hours. To the reaction mixture, after being cooled down to room temperature, 250 mL of water and 150 mL of toluene were added, and then hydrochloric acid was added to adjust the pH to 1.0. The aqueous layer was separated, adjusted to pH 10.0 with a 20% sodium hydroxide aqueous solution, and stirred at room temperature for 15 min and under cooling on ice for 30 min. The solid matter was collected by filtration and washed twice with 50 mL of water and twice with 50 mL of toluene to obtain 52.3 g of 4-{3-[4-(3-hydroxypropyl)-1-piperidinyl]propoxy}benzonitrile monohydrate as a white solid.

Workup

temperatureTo the reaction mixture, after being cooled down to room temperature
customThe aqueous layer was separated
stirringstirred at room temperature for 15 min
temperatureunder cooling on ice for 30 min
filtrationThe solid matter was collected by filtration
washwashed twice with 50 mL of water and twice with 50 mL of toluene

Sources & evidence

ORD record: ord-236e301dba894c7bb118600cfe5dbadb
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08536343B2

Reaction notes

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