Benzylamine → Carvedilol

HRID 1455621Notes

Reaction equation

HRID 1455621 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].C(COC)OC>[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 80711,2-DimethoxyethaneSolvent

Procedure

To 250 ml dimethoxyethane, 70 g (0.27 moles) of anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 10.25 g (0.075 moles) of anhydrous ZnCl2 and 50 g (0.21 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). Dimethoxyethane is distilled off from the reaction mixture and to the concentrated mass is added 400 ml ethylacetate, followed by 100 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, (7 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 (100 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (50 ml) and toluene (50 ml) to obtain carvedilol (50 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (45 g).

Workup

  1. distillationDimethoxyethane is distilled off from the reaction mixture and to the concentrated mass
  2. additionis added 400 ml ethylacetate
  3. customThe aqueous layer separated
  4. washis washed with water till neutral pH
  5. filtrationfiltered
  6. additionTo this solution of N-benzyl carvedilol in ethylacetate, (7 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added
  7. filtrationThe reaction mixture is filtered
  8. concentrationfiltrate concentrated
  9. customto remove ethylacetate
  10. additionTo the resultant syrupy mass n-butanol (100 ml) is added
  11. customthe crystals separated by filtration
  12. washwashed successively with n-butanol (50 ml) and toluene (50 ml)

Sources & evidence

ORD record
ord-13bb8bee095341a0811b20462121af32
Source dataset
uspto-grants-2009_01
Patent number
US07482471B2

Reaction notes

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