Benzylamine → Carvedilol

HRID 1455626Notes

Reaction equation

HRID 1455626 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>C(OC(=O)C)C.[Pd].[Cl-].[Cl-].[Zn+2]>[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

7

Reactant 3

HCID 7504BenzylamineHCID 50207104-Oxiranylmethoxy-9H-carbazoleHCID 110383641-{benzyl[2-(2-methoxyphenoxy)ethyl]amino}-3-(9H-carbazol-4-yloxy)propan-2-ol2×

Product 1

HCID 2585Carvedilol

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 3007855ZincchlorideCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

To 400 ml ethylacetate, 70 g (0.27 moles) 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 3 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture is cooled to ambient temperature and quenched into 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 and the filtrate subjected to hydrogenation reaction. 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 4.0 Kg/cm2 at temperature of 60-70° C. for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to about 3-4 volumes of the original volume and left for crystallisation of crude carvedilol for a period of about 10 hrs and filtered to obtain carvedilol (50 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (42 g).

Workup

  1. customquenched into 100 ml of ˜12-15% aqueous ammonia
  2. customThe aqueous layer separated
  3. washis washed with water till neutral pH
  4. filtrationfiltered
  5. customthe filtrate subjected to hydrogenation reaction
  6. filtrationThe reaction mixture is filtered
  7. concentrationfiltrate concentrated to about 3-4 volumes of the original volume
  8. waitleft for crystallisation of crude carvedilol for a period of about 10 hrs
  9. filtrationfiltered

Sources & evidence

ORD record
ord-d4539cb6ce61486cb7fe482ca7dc8b2d
Source dataset
uspto-grants-2009_01
Patent number
US07482471B2

Reaction notes

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