Water → (S)-4-[2-Hydroxy-3-([4-(4-carbamoylphenoxy)phenyl]-2-methylpropylamino)propoxy]carbazole

HRID 2227774Notes

Reaction equation

HRID 2227774 reaction equation
[O:1]1[CH2:3][C@H: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.NC(C)(C)C[C:22]1[CH:37]=[CH:36][C:25]([O:26][C:27]2[CH:35]=[CH:34][C:30]([C:31]([NH2:33])=[O:32])=[CH:29][CH:28]=2)=[CH:24][CH:23]=1.O>C(O)(=O)C.CO>[OH:1][C@@H:2]([CH2:3][N:11]([C:22]1[CH:23]=[CH:24][C:25]([O:26][C:27]2[CH:28]=[CH:29][C:30]([C:31](=[O:32])[NH2:33])=[CH:34][CH:35]=2)=[CH:36][CH:37]=1)[CH2:10][CH:18]([CH3:6])[CH3:17])[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

Participants

6

Reactant 3

HCID 962WaterHCID 10879208(S)-(+)-4-(2,3-Epoxypropoxy)carbazoleHCID 118329614-(4-(2-Amino-2-methylpropyl)phenoxy)benzamide2×

Product 1

HCID 53754997(S)-4-[2-Hydroxy-3-([4-(4-carbamoylphenoxy)phenyl]-2-methylpropylamino)propoxy]carbazoleYield 174.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A stirred mixture of (S)-(+)-4-(oxiranylmethoxy)-carbazole (7.50 g, 31.3 mmol), 4-(4-(2-amino-2-methylpropyl)-phenoxy)benzamide (17.82 g, 62.67 mmol), acetic acid (0.10 g, 1.7 mmol), water (10 mL) and methanol (260 mL) was heated to 60° C. for 22.7 hrs. The mixture was cooled and concentrated in vacuo to an oil. The concentrate was taken up in ethyl acetate (250 mL) and partitioned with water (100 mL). The organic layer was then extracted with a solution of 25 mL 1N HCl (25 mL) in water (35 mL). A white precipitate formed during the extraction was mostly 4-(4-(2-amino-2-methylpropyl)-phenoxy)benzamide and was removed by filtration of the two phase mixture. The organic layer was extracted two times with a solution of 1N HCl (3 mL) in water (50 mL). The ethyl acetate layer was stripped to an oily residue. The crude product was purified by flash chromatography with 416 g 230-400 silica gel and eluting with ethyl acetate then 10:1-3 ethyl acetate:ethanol gradient. Concentration of the appropriate fractions and drying under vacuum gave 14.31 g (87.2%) of the desired product as a foamy white solid. 1H NMR was consistent with the desired compound.

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated in vacuo to an oil
  3. custompartitioned with water (100 mL)
  4. extractionThe organic layer was then extracted with a solution of 25 mL 1N HCl (25 mL) in water (35 mL)
  5. customA white precipitate formed during the extraction
  6. customwas removed by filtration of the two phase mixture
  7. extractionThe organic layer was extracted two times with a solution of 1N HCl (3 mL) in water (50 mL)
  8. customThe crude product was purified by flash chromatography with 416 g 230-400 silica gel
  9. washeluting with ethyl acetate
  10. customConcentration of the appropriate fractions and drying under vacuum

Sources & evidence

ORD record
ord-71f484761ebc43e8ab217cc610a07d3a
Source dataset
uspto-grants-2002_07
Patent number
US06413991B1

Reaction notes

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