Calcium Carbonate → Carvedilol

HRID 493434Notes

Reaction equation

HRID 493434 reaction equation
[O:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH:9]=[CH:8][CH:7]=1.O.Cl.[CH3:21][O:22][C:23]1[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=1[O:25][CH2:26][CH2:27][NH2:28].C(=O)([O-])[O-].[Ca+2]>C(O)(C)C>[CH3:21][O:22][C:23]1[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=1[O:25][CH2:26][CH2:27][NH:28][CH2:3][CH:2]([OH:1])[CH2:4][O:5][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[NH:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:18]=12

Participants

5

Reactant 3

HCID 10112Calcium CarbonateHCID 50207104-Oxiranylmethoxy-9H-carbazoleHCID 60145921HCID 60145921, compound

Product 1

HCID 2585Carvedilol

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 43.2 g 4-(oxirane-2-ylmethoxy)-9H-carbazole (II), 80.0 g of 2-(2-methoxyphenoxy)ethylamine hydrogenchloride monohydrate (IV) and 52.4 g of anhydrous calcium carbonate in 330 ml isopropanol is, with intensive stirring, heated at 80° C. for 4 hours. When the epoxide has reacted, the mixed salts are filtered off from the reaction mixture and isopropanol is distilled off from the filtrate. The obtained honey-like concentrate is dissolved, when hot, in 210 ml of ethylacetate, the solution is cooled to the temperature of 40° C., inoculated and stirred at the temperature of 40° C. for 30 minutes. After the crystal precipitates, the mixture is cooled to 0° C., and is kept like that with stirring for a minimum of four hours. After filtration and washing with cooled ethylacetate, 65 to 70 g of wet crude Carvedilol is obtained (HPLC contents>98 area %, HPLC contents of the bis-derivative 1.2-1.5 area %).

Workup

  1. filtrationthe mixed salts are filtered off from the reaction mixture and isopropanol
  2. distillationis distilled off from the filtrate
  3. concentrationThe obtained honey-like concentrate
  4. dissolutionis dissolved
  5. temperaturewhen hot, in 210 ml of ethylacetate, the solution is cooled to the temperature of 40° C.
  6. customAfter the crystal precipitates
  7. temperaturethe mixture is cooled to 0° C.
  8. stirringthat with stirring for a minimum of four hours
  9. filtrationAfter filtration
  10. washwashing with cooled ethylacetate

Sources & evidence

ORD record
ord-49947de7881740dea579d81cb9e25af0
Source dataset
uspto-grants-2009_05
Patent number
US07534895B2

Reaction notes

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