Ethyl bromoacetate → HCID 68900879, compound

HRID 1985026Notes

Reaction equation

HRID 1985026 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:24])[CH2:9][NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=3)[CH2:12]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([OH:43])=[O:42]>C(C(C)=O)C>[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]\[C:41]([OH:43])=[O:42].[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:24])[CH2:9][NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[O:23][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:12]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 444266Maleic AcidHCID 68901479HCID 68901479, compound

Product 1

HCID 68900879HCID 68900879, compound

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent3×

Procedure

A methyl ethyl ketone mixture liquid of 1 equivalent of (1R)-1-(3-chlorophenyl)-2-[(1R,3R)-3-(3-hydroxyphenyl)cyclohexylamino]ethanol 1/3 toluene-solvate and from 2.0 to 3.0 equivalents of potassium carbonate was heated under reflux. With heating, a methyl ethyl ketone solution of from 1.0 to 1.2 equivalents of ethyl bromoacetate was dropwise added to the mixture liquid, and further heated under reflux for 3 to 4 hours. A part of the reaction liquid was sampled, and subjected to HPLC analysis. After cooled, this was filtered through Celite, and a methyl ethyl ketone solution of 1.0 equivalent of maleic acid was put into the obtained solution, and stirred. The precipitated crystal was taken out through filtration, and dried through aeration to obtain ethyl 3-[(1R,3R)-3-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]cyclohexyl]phenoxyacetate maleate. The obtained crystal was subjected to HPLC analysis, in which the content of (1R)-1-(3-chlorophenyl)-2-[(1R,3R)-3-(3-hydroxyphenyl)cyclohexylamino]ethanol (starting compound) and the content of ethyl 3-[(1R,3R)-3-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]cyclohexyl]phenoxyacetate (target product) in the crystal were determined according to the above-mentioned relative area percentage method.

Workup

  1. temperatureunder reflux
  2. temperatureWith heating
  3. temperaturefurther heated
  4. temperatureunder reflux for 3 to 4 hours
  5. customA part of the reaction liquid
  6. aliquotwas sampled
  7. temperatureAfter cooled
  8. filtrationthis was filtered through Celite
  9. filtrationThe precipitated crystal was taken out through filtration
  10. customdried through aeration

Sources & evidence

ORD record
ord-52a996587da64933acda25c14659d239
Source dataset
uspto-grants-2009_06
Patent number
US07544841B2

Reaction notes

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