Ethyl bromoacetate → HCID 68900879, compound

HRID 1985027Notes

Reaction equation

HRID 1985027 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 3.0 equivalents of potassium carbonate was heated under reflux for 2 hours. With heating, a methyl ethyl ketone solution of 1.2 equivalents of ethyl bromoacetate was dropwise added to the mixture liquid, and further heated under reflux for 3 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 at room temperature for 30 minutes, and then, with cooling with ice, for 30 minutes. The precipitated crystal was taken out through filtration, then washed with methyl ethyl ketone, 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 for 2 hours
  2. temperatureWith heating
  3. temperaturefurther heated
  4. temperatureunder reflux for 3 hours
  5. customA part of the reaction liquid
  6. aliquotwas sampled
  7. temperatureAfter cooled
  8. filtrationthis was filtered through Celite
  9. temperaturewith cooling with ice, for 30 minutes
  10. filtrationThe precipitated crystal was taken out through filtration
  11. washwashed with methyl ethyl ketone
  12. customdried through aeration

Sources & evidence

ORD record
ord-3dbff2aa6fd7483d8de868f3bb1fedf3
Source dataset
uspto-grants-2009_06
Patent number
US07544841B2

Reaction notes

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