Hydrogen Bromide → Tolterodine

HRID 916310Notes

Reaction equation

HRID 916310 reaction equation
[CH:1]([N:4]([CH:23]([CH3:25])[CH3:24])[CH2:5][CH2:6][CH:7]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1[O:21]C)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:3])[CH3:2].C(N(C(C)C)CCC(C1C=C(OC)C=CC=1C)C1C=CC=CC=1)(C)C.Br>C(O)(=O)C>[CH3:20][C:18]1[CH:17]=[CH:16][C:15]([OH:21])=[C:14]([C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH:23]([CH3:24])[CH3:25])[CH:19]=1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 9923998(3RS)-3-(2-Methoxy-5-methylphenyl)-N,N-bis(1-methylethyl)-3-phenylpropan-1-amineHCID 25023433N,N-diisopropyl-3-(5-methoxy-2-methylphenyl)-3-phenylpropanamine

Product 1

HCID 443879TolterodineYield 85.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

N,N-diisopropyl-3(2-methoxy-5-methylphenyl)-3-phenylpropanamine and N,N-diisopropyl-3-(5-methoxy-2-methylphenyl)-3-phenylpropanamine (11.0 g, 32.4 mmol) was dissolved in acetic acid (15 ml). After addition of 47% aqueous hydrobromic acid (25 ml), the mixture was heated to reflux for three hours (bath temperature, 120° C.). The reaction mixture was cooled to the room temperature. After the solvent was distilled off, water (120 ml) and toluene (110 ml) were added to the residue, to which sodium hydroxide (2.2 g) and sodium carbonate (26 g) were added to adjust pH to 11. After the aqueous layer was phase-separated to remove, the organic layer was washed with an aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent in the dried solution was distilled off under reduced pressure to obtain 9.04 g of racemic tolterodine (yield 85.7%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureThe reaction mixture was cooled to the room temperature
  3. distillationAfter the solvent was distilled off
  4. additionwater (120 ml) and toluene (110 ml) were added to the residue, to which sodium hydroxide (2.2 g) and sodium carbonate (26 g)
  5. additionwere added
  6. customAfter the aqueous layer was phase-separated
  7. customto remove
  8. washthe organic layer was washed with an aqueous sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationThe solvent in the dried solution was distilled off under reduced pressure

Sources & evidence

ORD record
ord-565da2f1447041349ee4085f64daac52
Source dataset
uspto-grants-2007_09
Patent number
US07268257B1

Reaction notes

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