Isobutyryl chloride → Fesoterodine

HRID 1669967Notes

Reaction equation

HRID 1669967 reaction equation
[C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].[CH:7]([N:10]([CH:29]([CH3:31])[CH3:30])[CH2:11][CH2:12][C@@H:13]([C:20]1[CH:25]=[C:24]([CH2:26][OH:27])[CH:23]=[CH:22][C:21]=1[OH:28])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:9])[CH3:8]>ClCCl>[CH3:3][CH:2]([C:1]([O:28][C:21]1[CH:22]=[CH:23][C:24]([CH2:26][OH:27])=[CH:25][C:20]=1[C@@H:13]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:12][CH2:11][N:10]([CH:7]([CH3:9])[CH3:8])[CH:29]([CH3:31])[CH3:30])=[O:5])[CH3:4]

Participants

4

Reactant 2

HCID 62325Isobutyryl chlorideHCID 9819382(R)-5-Hydroxymethyltolterodine

Product 1

HCID 6918558Fesoterodine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-3 °C

Procedure

Drops of a solution of 18.6 g isobutyric acid chloride in 250 ml dichloromethane were added in approximately 10 minutes to a solution of 59.8 g (175.1 mol) (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol cooled to −3° C. (A, see FIG. 1) dissolved in 750 ml dichloromethane with agitation and cooling by ice bath. A white substance precipitated after approximately 5 minutes. For this purpose drops of a solution of 17.7 g triethylamine in 250 ml dichloromethane were added in 5 minutes under agitation and ice bath cooling. The batch was washed once with each of 250 ml water, 250 ml approximate 5% aqueous NaHCO3 solution and 250 ml water. The dichloromethane extract dried over Na2SO4 was evaporated to a low small bulk on a rotary evaporator to constant weight, whereby a pale yellow, high viscosity oil was left.

Workup

  1. temperaturecooling by ice bath
  2. customA white substance precipitated after approximately 5 minutes
  3. additionwere added in 5 minutes under agitation and ice bath
  4. temperaturecooling
  5. washThe batch was washed once with each of 250 ml water, 250 ml approximate 5% aqueous NaHCO3 solution and 250 ml water
  6. extractionThe dichloromethane extract
  7. dry with materialdried over Na2SO4
  8. customwas evaporated to a low small bulk on a rotary evaporator to constant weight, whereby a pale yellow, high viscosity oil
  9. waitwas left

Sources & evidence

ORD record
ord-7e581be49d7140eb82f06fb4839a9df1
Source dataset
uspto-grants-2011_08
Patent number
US07989654B2

Reaction notes

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