Acetic Acid → Carvedilol

HRID 1455625Notes

Reaction equation

HRID 1455625 reaction equation
C(N)C1C=CC=CC=1.C(O)(=O)C.O1CC1COC1C2C3C(=CC=CC=3)NC=2C=CC=1.[CH3:31][O:32][C:33]1[C:38]([O:39][CH2:40][CH2:41][N:42]([CH2:50][CH:51]([OH:67])[CH2:52][O:53][C:54]2[C:59]3[C:60]4[C:65]([NH:66][C:58]=3[CH:57]=[CH:56][CH:55]=2)=[CH:64][CH:63]=[CH:62][CH:61]=4)CC2C=CC=CC=2)=[CH:37][CH:36]=[CH:35][CH:34]=1>C1OCCOC1>[CH3:31][O:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:38]=1[O:39][CH2:40][CH2:41][NH:42][CH2:50][CH:51]([OH:67])[CH2:52][O:53][C:54]1[CH:55]=[CH:56][CH:57]=[C:58]2[NH:66][C:65]3[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=3[C:59]=12

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 7504BenzylamineHCID 50207104-Oxiranylmethoxy-9H-carbazole2×HCID 110383641-{benzyl[2-(2-methoxyphenoxy)ethyl]amino}-3-(9H-carbazol-4-yloxy)propan-2-ol2×

Product 1

HCID 2585Carvedilol

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To 5 ml dioxane 1.4 g (0.0054 moles) of anhydrous N-2-[2-(methoxy)-phenoxy]-ethyl]-benzylamine, 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is heated to 70-75° C. for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) of 4-(oxiranylmethoxy)-9H-carbazole are added and the reaction mixture is further heated to 70-75° C. for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). Dioxane is distilled off from the reaction mixture and to the concentrated reaction mixture 10 ml ethylacetate is added and subjected the reaction mass to hydrogenation. 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 8 hours. The reaction mixture is filtered and the filtrate is washed with 12-15% v/v aqueous ammonia (1 volume w. r .t. to the carbazole). The product enriched organic layer is separated and 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 (0.75 g).

Workup

  1. additionare added
  2. distillationDioxane is distilled off from the reaction mixture and to the concentrated reaction mixture 10 ml ethylacetate
  3. additionis added
  4. 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
  5. filtrationThe reaction mixture is filtered
  6. washthe filtrate is washed with 12-15% v/v aqueous ammonia (1 volume w
  7. customis separated
  8. concentrationconcentrated
  9. customto remove ethylacetate
  10. additionTo the resultant syrupy mass n-butanol (2 ml) is added
  11. customthe crystals separated by filtration
  12. washwashed successively with n-butanol (1 ml) and toluene (1 ml)

Sources & evidence

ORD record
ord-6ef4a3d5dee74105afceffa3449b6cba
Source dataset
uspto-grants-2009_01
Patent number
US07482471B2

Reaction notes

Loading…