Benzylamine → Carvedilol

HRID 1455622Notes

Reaction equation

HRID 1455622 reaction equation
C(N)C1C=CC=CC=1.O1CC1COC1C2C3C(=CC=CC=3)NC=2C=CC=1.[CH3:27][O:28][C:29]1[C:34]([O:35][CH2:36][CH2:37][N:38]([CH2:46][CH:47]([OH:63])[CH2:48][O:49][C:50]2[C:55]3[C:56]4[C:61]([NH:62][C:54]=3[CH:53]=[CH:52][CH:51]=2)=[CH:60][CH:59]=[CH:58][CH:57]=4)CC2C=CC=CC=2)=[CH:33][CH:32]=[CH:31][CH:30]=1>[Cl-].[Cl-].[Zn+2].C1OCCOC1>[CH3:27][O:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:34]=1[O:35][CH2:36][CH2:37][NH:38][CH2:46][CH:47]([OH:63])[CH2:48][O:49][C:50]1[CH:51]=[CH:52][CH:53]=[C:54]2[NH:62][C:61]3[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=3[C:55]=12

Participants

6

Reactant 3

HCID 7504BenzylamineHCID 50207104-Oxiranylmethoxy-9H-carbazoleHCID 110383641-{benzyl[2-(2-methoxyphenoxy)ethyl]amino}-3-(9H-carbazol-4-yloxy)propan-2-ol

Product 1

HCID 2585Carvedilol

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

To 5 ml Dioxane 1.4 g (0.0054 moles) of anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 0.21 g (0.0015 moles) of anhydrous ZnCl2 and 1 g (0.0042 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is heated to 70-75° C. for 2.5 hrs (TLC control for checking conversion to N-benzyl carvedilol). The dioxane is distilled off from the reaction mixture and to the concentrated mass is added 10 ml ethylacetate, followed by 2 ml of ˜12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4.5 Kg/cm2 at temperature of 60-70° C. for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.8 g).

Workup

  1. additionare added
  2. distillationThe dioxane is distilled off from the reaction mixture and to the concentrated mass
  3. additionis added 10 ml ethylacetate
  4. customThe aqueous layer separated
  5. washis washed with water till neutral pH
  6. filtrationfiltered
  7. additionTo this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added
  8. filtrationThe reaction mixture is filtered
  9. concentrationfiltrate concentrated
  10. customto remove ethylacetate
  11. additionTo the resultant syrupy mass n-butanol (2 ml) is added
  12. customthe crystals separated by filtration
  13. washwashed successively with n-butanol (1 ml) and toluene (1 ml)

Sources & evidence

ORD record
ord-1636e59023bf48808bb2771b1cdcf00d
Source dataset
uspto-grants-2009_01
Patent number
US07482471B2

Reaction notes

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