Hydrogen Bromide → Darifenacin nitrile hydrobromide

HRID 585179Notes

Reaction equation

HRID 585179 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][C@@H:14]([C:17]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18]#[N:19])[CH2:13]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1.[BrH:32]>CO>[BrH:32].[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][C@@H:14]([C:17]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18]#[N:19])[CH2:13]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 24860221(S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetonitrile

Product 1

HCID 24860222Darifenacin nitrile hydrobromideYield 93.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a slurry of (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetonitrile (V) (30.0 g, 0.073 moles) in methanol (150 mL) is added 48% aqueous hydrobromic acid (13.6 g, 0.081 moles) maintaining the temperature below 40° C. The mixture is heated at reflux for 1 hour. The batch is cooled to 0° C., and the product is collected by filtration, washed with methanol (60 mL) and dried at 50° C. under vacuum to give (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetonitrile hydrobromide (VI) (33.5 g, 93%).

Workup

  1. temperaturemaintaining the temperature below 40° C
  2. temperatureThe mixture is heated
  3. temperatureat reflux for 1 hour
  4. filtrationthe product is collected by filtration
  5. washwashed with methanol (60 mL)
  6. customdried at 50° C. under vacuum

Sources & evidence

ORD record
ord-9a51d63cfe4f43bea2c397f2e73a4417
Source dataset
uspto-grants-2005_08
Patent number
US06930188B2

Reaction notes

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