Sulfuric Acid → 1-[2-(4-Benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea Sulfate Trihydrate

HRID 563933Notes

Reaction equation

[CH2:1]([C:8]1([OH:31])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][NH:16][C:17]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)=[O:18])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:32](=[O:36])(=[O:35])([OH:34])[OH:33]>C(O)C>[OH2:18].[OH2:33].[OH2:18].[S:32]([OH:36])([OH:35])(=[O:34])=[O:33].[CH2:1]([C:8]1([OH:31])[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][NH:16][C:17]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)=[O:18])[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea (15.4 kg, 1 equivalent) is dissolved in ethanol (78 L) and the mixture is heated at 50° C. Aqueous sulfuric acid (1M, 1.1 equivalents) is added during 35 minutes. The crystallization is initiated by a wet seed of Example 1 (1%) as described below. The suspension is cooled to 1° C. with a cooling rate of 14° C./h and maintained at this temperature at least 11 hours before filtration and washing with aqueous ethanol (50% W/W, 50 L). The solid is dried at 30° C. under a wet stream of nitrogen (33-40% RH) to provide the title compound with a purity of 99.4% with a yield of approximately 79%.

Workup

customThe crystallization
temperatureThe suspension is cooled to 1° C. with a cooling rate of 14° C./h
temperaturemaintained at this temperature at least 11 hours before filtration
washwashing with aqueous ethanol (50% W/W, 50 L)
customThe solid is dried at 30° C. under a wet stream of nitrogen (33-40% RH)

Sources & evidence

ORD record: ord-ade1872da1194212a4502a69ce940759
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067601B2

Reaction notes

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