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Methanol → 4-(2,4-dichlorophenyl)-5-methyl-2-{N-{alpha-cyclopropyl-4-[3-(chloromethyl)benzoyloxymethyl]benzyl}-N-propylamino}thiazole

HRID 399634
Notes
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Reaction equation

HRID 399634 reaction equation
[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7].[Cl:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[C:20]1[N:21]=[C:22]([N:26]([CH:30]([CH:39]2[CH2:41][CH2:40]2)[C:31]2[CH:36]=[CH:35][C:34]([CH2:37][OH:38])=[CH:33][CH:32]=2)[CH2:27][CH2:28][CH3:29])[S:23][C:24]=1[CH3:25].CO>N1C=CC=CC=1.C(Cl)Cl>[Cl:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[C:20]1[N:21]=[C:22]([N:26]([CH:30]([CH:39]2[CH2:40][CH2:41]2)[C:31]2[CH:32]=[CH:33][C:34]([CH2:37][O:38][C:6](=[O:7])[C:5]3[CH:9]=[CH:10][CH:11]=[C:3]([CH2:2][Cl:1])[CH:4]=3)=[CH:35][CH:36]=2)[CH2:27][CH2:28][CH3:29])[S:23][C:24]=1[CH3:25]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 887MethanolHCID 27333243-(Chloromethyl)benzoyl chlorideHCID 152916114-(2,4-dichlorophenyl)-5-methyl-2-{N-[alpha-cyclopropyl-4-(hydroxymethyl)benzyl]N-propylamino}thiazole

Product 1

HCID 189678354-(2,4-dichlorophenyl)-5-methyl-2-{N-{alpha-cyclopropyl-4-[3-(chloromethyl)benzoyloxymethyl]benzyl}-N-propylamino}thiazoleYield 81%

Reagents, catalysts & solvents 2

HCID 1049
Pyridine
Solvent
HCID 6344DichloromethaneSolvent

Procedure

0.6 ml of 3-chloromethylbenzoyl chloride is added dropwise, at 0° C., to 1.6 g of the compound of Example 4 dissolved in 10 ml of anhydrous pyridine. After 2 hours at 0° C., methanol is added to hydrolyze the excess acid chloride and the organic phase is diluted with methylene chloride. This is then washed with 2N hydrochloric acid, with saturated aqueous sodium bicarbonate and then with saturated aqueous sodium chloride and dried over anhydrous sodium sulphate. The organic solvent is evaporated off and the product is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent, to give the expected product.

Workup

  1. washThis is then washed with 2N hydrochloric acid, with saturated aqueous sodium bicarbonate
  2. dry with materialwith saturated aqueous sodium chloride and dried over anhydrous sodium sulphate
  3. customThe organic solvent is evaporated off
  4. customthe product is purified on a column of silica
  5. additiona mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent

Sources & evidence

ORD record
ord-c3abf37985a04eedbdaced9381a9dde5
Source dataset
uspto-grants-1998_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05821255

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes