Hydrochloric Acid → Carvedilol

HRID 47912Notes

Reaction equation

HRID 47912 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][CH2:7][NH2:8].[O:13]1[CH2:15][CH:14]1[CH2:16][O:17][C:18]1[C:30]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][C:22]=2[CH:21]=[CH:20][CH:19]=1.O.Cl>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][CH2:7][NH:8][CH2:15][CH:14]([OH:13])[CH2:16][O:17][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[NH:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=3[C:30]=12

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 17130052-(2-Methoxyphenoxy)ethyl amineHCID 50207104-Oxiranylmethoxy-9H-carbazole

Product 1

HCID 2585Carvedilol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

2-(2-Methoxyphenoxy)ethylamine (III) (4.89 g) was heated to about 100° C., after which 4-(oxiran-2-ylmethoxy)-9H-carbazole (II) (3.31 g) was added portionwise. After approximately 20 minutes, the reaction mixture was cooled to about 70° C., after which water (25 ml) and ethyl acetate (15 ml) were added. The pH of the two-phase mixture was then adjusted to 5 with 2 N hydrochloric acid. The solid that formed, Carvedilol hydrochloride hydrate, is filtered, washed with water (20 ml) followed with ethylacetate (15 ml). The resulting material is reslurried in ethylacetate (50 ml) and water (20 ml) containing 5% Sodium carbonate until the pH reached 7.5. The organic phase was separated and dried over sodium sulfate. The dried solution was concentrated to a turbid solution and cooled overnight to about 4° C. Precipitated carvedilol was isolated by filteration and crystallized from isopropanol.

Workup

  1. customThe solid that formed
  2. filtrationCarvedilol hydrochloride hydrate, is filtered
  3. washwashed with water (20 ml)
  4. additionwater (20 ml) containing 5% Sodium carbonate until the pH
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. concentrationThe dried solution was concentrated to a turbid solution
  8. temperaturecooled overnight to about 4° C

Sources & evidence

ORD record
ord-0152c08a876b474d83d17e513a1cce0a
Source dataset
uspto-grants-2004_03
Patent number
US06699997B2

Reaction notes

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