[2-[(1R)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylpropanoate

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 15.1 g (36.6 mmols) of fesoterodine are loaded into a 1 liter flask, followed by 4.25 g (36.6 mmols) of fumaric acid and 450 ml of deionised water. The mixture is stirred at 40° C. until complete dissolution of the solids and filtered over a 0.45 micron filter. The solution is then divided in equal parts and loaded into three 1000 ml flasks. Each flask is connected to a rotavapor without activating the vacuum and under rotation each flask is immersed in a dry ice and acetone bath kept at −50° C. Each flask is left in such conditions for two hours, until a uniform layer of frozen material is obtained on the inner surface of each flask. The three flasks are then connected to a lyophilisation apparatus CHRIST Alpha 1-4 LSC and their content is lyophilized. The conditions used were the following: filtered over a 0.45 micron filter Each flask is connected to a rotavapor kept at −50° C is obtained on the inner surface of each flask

Conditions: temp:-3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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 sallow, high viscosity oil was left. Raw yield: 63.7 g (88.5% of the theory). 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 sallow, high viscosity oil was left

Conditions: temp:-3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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 sallow, high viscosity oil was left. 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 sallow, high viscosity oil was left

Conditions: temp:-3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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. cooling by ice bath A white substance precipitated after approximately 5 minutes 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

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 7% solution of aqueous NaHCO3 (25 ml) was added to a suspension of Fesoterodine Hydrochloride monohydrate (5 g) in dichloromethane (50 ml) at 10-15° C. The resulting mixture was stirred at room temperature and the two phases were separated. The organic phase was evaporated under reduced pressure; acetone (10 ml) was added twice and evaporated under reduced pressure to afford a Fesoterodine base solution. The Fesoterodine base solution was added over an acetone/fumaric acid suspension (10 ml/1.25 g) at 15-20° C. Diisopropyl ether 5 ml was added at 10-15° C. and the suspension was stirred to allow crystallization for 1-2 h, then diisopropyl ether 5 ml was added and the suspension stirred for 1-2 h. Finally diisopropyl ether (30 ml) was added and the suspension stirred for another 1-2 h. The suspension was filtered off and the crystallized product was washed with acetone/diisopropyl ether (10 ml), to yield 5.1 g of the corresponding Fesoterodine Fumarate. crystallization for 1-2 h diisopropyl ether 5 ml was added the suspension stirred for 1-2 h Finally diisopropyl ether (30 ml) was added the suspension stirred for another 1-2 h The suspension was filtered off the crystallized product was washed with acetone/diisopropyl ether (10 ml)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 42 g Fesoterodine of formula (J) in 240 ml IPA (240 ml) is added at 25° C. to 30° C. and then heated to 50° C. to 55° C. Fumaric acid (17 g) was added to the resulting mass was maintained for 30 minutes and further cooled to 25° C. to 30° C. followed by the addition of diisopropyl ether (840 ml) at 25° C. to 30° C. and maintained for 12 hours. The resulting mass was filtered, washed with diisopropyl ether (2×30 ml) and then dried under vacuum for 24 hours at 45° C. to 50° C. to afford Fesoterodine Fumarate (70 g) (Purity by HPLC: 99.98%). heated to 50° C. to 55° C was maintained for 30 minutes further cooled to 25° C. to 30° C. maintained for 12 hours The resulting mass was filtered washed with diisopropyl ether (2×30 ml) dried under vacuum for 24 hours at 45° C. to 50° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Fesoterodine base (5 g) and ethyl acetate (20 ml) were added to a four-neck two liter round bottom flask. Further, 2-chloro-mandelic acid (2.3 g) was added at 25° C. to 35° C. The reaction mass was stirred for 2 hours at 25° C. to 35° C. The reaction mass was cooled to 0° C. to 5° C. The product was filtered and washed with chilled ethyl acetate (2×2.5 ml). The wet cake was dried at 60° C. to 65° C. for 8 to 10 to afford solid fesoterodine 2-chloro-mandelate (Purity by HPLC: 99.8%). The reaction mass was cooled to 0° C. to 5° C The product was filtered washed with chilled ethyl acetate (2×2.5 ml) The wet cake was dried at 60° C. to 65° C. for 8 to 10

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 42 g Fesoterodine in 90 ml methyl ethyl ketone was stirred with 12 g fumaric acid at 80° C. for 1 hour. This was followed by the slow addition of 30 ml cyclohexane under stirring and further stirred for 1 hour at 80° C. The solution was cooled slowly to 25° C. to 30° C. and stirred for 6 hours at the same temperature. The solution was further cooled at 0° C. to 50° C. C and stirred for overnight. The separated solid was filtered and washed with mixture of cyclohexane and methyl ethyl ketone mixture to give Fesoterodine Fumarate wherein impurity X is 0.03%. further stirred for 1 hour at 80° C The solution was cooled slowly to 25° C. to 30° C. stirred for 6 hours at the same temperature The solution was further cooled at 0° C. to 50° C C and stirred for overnight The separated solid was filtered washed with mixture of cyclohexane and methyl ethyl ketone mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 42 g Fesoterodine of formula (J) in 90 ml methyl ethyl ketone was stirred with 12 g fumaric acid at 80° C. for 1 hour. This was followed by the slow addition of 30 ml cyclohexane under stirring and further stirred for 1 hour at 80° C. The solution was cooled slowly to 25° C. to 30° C. and stirred for 6 hours at the same temperature. The solution was further cooled at 0° C. to 50° C. C and stirred for overnight. The separated solid was filtered and washed with mixture of cyclohexane and methyl ethyl ketone mixture to give fesoterodine fumarate. further stirred for 1 hour at 80° C The solution was cooled slowly to 25° C. to 30° C. stirred for 6 hours at the same temperature The solution was further cooled at 0° C. to 50° C C and stirred for overnight The separated solid was filtered washed with mixture of cyclohexane and methyl ethyl ketone mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The fesoterodine of formula (J) is converted into fumarate salt by reacting with fumaric acid in the presence of solvent such as 2-butanone and cyclohexane to obtain pure fesoterodine fumarate.

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 15.1 g (36.6 mmols) of fesoterodine are loaded into a 1 liter flask, followed by 4.25 g (36.6 mmols) of fumaric acid and 450 ml of deionised water. The mixture is stirred at 40° C. until complete dissolution of the solids and filtered over a 0.45 micron filter. The solution is then divided in equal parts and loaded into three 1000 ml flasks. Each flask is connected to a rotavapor without activating the vacuum and under rotation each flask is immersed in a dry ice and acetone bath kept at −50° C. Each flask is left in such conditions for two hours, until a uniform layer of frozen material is obtained on the inner surface of each flask. The three flasks are then connected to a lyophilisation apparatus CHRIST Alpha 1-4 LSC and their content is lyophilized. The conditions used were the following: filtered over a 0.45 micron filter Each flask is connected to a rotavapor kept at −50° C is obtained on the inner surface of each flask