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

HRID 563934Notes

Reaction equation

HRID 563934 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

4

Reactant 2

HCID 1118Sulfuric AcidHCID 10173280Palosuran

Product 1

HCID 116066021-[2-(4-Benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea Sulfate TrihydrateYield 94%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

1-[2-(4-Benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea (1.01 kg, 1 equivalent) is dissolved in ethanol (3.05 kg) under stirring (200±20 rpm) and the mixture is heated at 50° C. Aqueous sulfuric acid (1M, 1.1 equivalents) is added during 20 minutes. The crystallization is initiated by a wet seed of Example 1 (1%) as described below. The obtained mixture is maintained at 50° C. for about 15 minutes, then it is cooled to 0° C. with a cooling rate of 15° C./h and maintained at this temperature for least 1 hour before filtration and washing with aqueous ethanol (50% W/W, 3 kg). The solid is dried in a conductive agitated dryer at a temperature of 35±3° C. under a wet stream of nitrogen (45±5% RH), optionally under stirring (max. 70 rpm) in case the cake humidity is below 25%, to provide the title compound with a purity of 99.8% with a yield of approximately 94%.

Workup

  1. customThe crystallization
  2. temperatureThe obtained mixture is maintained at 50° C. for about 15 minutes
  3. temperatureit is cooled to 0° C. with a cooling rate of 15° C./h
  4. temperaturemaintained at this temperature for least 1 hour before filtration
  5. washwashing with aqueous ethanol (50% W/W, 3 kg)
  6. customThe solid is dried in a conductive agitated dryer at a temperature of 35±3° C. under a wet stream of nitrogen (45±5% RH)
  7. stirringoptionally under stirring (max. 70 rpm) in case the cake humidity is below 25%

Sources & evidence

ORD record
ord-c860aff491c6426ea60b342cd271161a
Source dataset
uspto-grants-2011_11
Patent number
US08067601B2

Reaction notes

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