2-(2,3-dichlorophenyl)acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To guanidine hydrochloride (25.4 kg, 266 mole) in methanol (60 litres) was added 30% w/w sodium methoxide in methanol solution (49.2 kg, 273.3 mole). The suspension was heated to 55° C.±2° C. The toluene solution of 2-(2,3-dichlorophenyl)-3-ethoxy-4-fluoro-2-butenenitrile was added over a period of 45 minutes and the resultant mixture was boiled under reflux for 4 hours, cooled then quenched into water (230 litres). The solid precipitate was washed with 5 portions of methanol (25 litres) to yield the racemate as an off white solid (26.3 kg, 38% yield from 2,3-dichlorophenylacetonitrile). The suspension was heated to 55° C.±2° C under reflux for 4 hours cooled then quenched into water (230 litres) The solid precipitate was washed with 5 portions of methanol (25 litres)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of NaOEt (from 3.63 gms Na) in ethanol (500 ml) was added 2,3-dichlorophenylacetonitrile (Example 14.3) in ethanol (150 ml). Ethyl formate (16.67 gms) was then added and the mixture stirred at 80° C. for 45 minutes, before adding a further quantity of ethyl formate (2.78 gms). After stirring at 80° C. for a further 1.5 hours, the precipitate was filtered off and dried in vacuo. The solid was dissolved in water, filtered, acidified with concentrated hydrochloric acid and the precipitate filtered off and dried in vacuo, 14.35 gms, 45% yield. After stirring at 80° C. for a further 1.5 hours the precipitate was filtered off dried in vacuo The solid was dissolved in water filtered the precipitate filtered off dried in vacuo, 14.35 gms, 45% yield

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

Procedure: This compound was made in an analogous manner to the compound of Example 6 from 2,3-dichlorophenylacetonitrile, m.pt. 245°-247° C.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of NaOEt (from 3.63 gms Na) in ethanol (500 ml) was added 2,3-dichlorophenylacetonitrile (Example 14.3) in ethanol (150 ml). Ethyl formate (16.67 gms) was then added and the mixture stirred at 80° C. for 45 minutes, before adding a further quantity of ethyl formate (2.78 gms). After stirring at 80° C. for a further 1.5 hours, the precipitate was filtered off and dried in vacuo. The solid was dissolved in water, filtered, acidified with concentrated hydrochloric acid and the precipitate filtered off and dried in vacuo, 14.35 gms, 45% yield. After stirring at 80° C. for a further 1.5 hours the precipitate was filtered off dried in vacuo The solid was dissolved in water filtered the precipitate filtered off dried in vacuo, 14.35 gms, 45% yield

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of NaOEt (from 3.63 gms Na) in ethanol (500 ml) was added 2,3-dichlorophenylacetonitrile (Example 14.3) in ethanol (150 ml). Ethyl formate (16.67 gms) was then added and the mixture stirred at 80° C. for 45 minutes, before adding a further quantity of ethyl formate (2.78 gms). After stirring at 80° C. for a further 1.5 hours, the precipitate was filtered off and dried in vacuo. The solid was dissolved in water, filtered, acidified with concentrated hydrochloric acid and the precipitate filtered off and dried in vacuo, 14.35 gms, 45% yield. After stirring at 80° C. for a further 1.5 hours the precipitate was filtered off dried in vacuo The solid was dissolved in water filtered the precipitate filtered off dried in vacuo, 14.35 gms, 45% yield

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

Procedure: Sodium (1.2 g) was added portionwise to ethanol (50 ml) with stirring. After the sodium had dissolved a solution of 2,3-dichlorophenylacetonitrile (9.4 g) in diethylcarbonate (25 ml) was added dropwise. The reaction mixture was heated until EtOH distilled over. The rate of addition was controlled such that it equalled the rate of distillation. After the completion of the addition, the reaction mixture was heated and distilled for a further 4 hours. The cooled reaction mixture was partitioned between water and EtOAc (300 ml each). The organic layer was dried and evaporated in vacuo and the residue was purified by flash column chromatography to give the title product. (5 g, 39%). was added dropwise distilled over The rate of addition the rate of distillation After the completion of the addition the reaction mixture was heated distilled for a further 4 hours The cooled reaction mixture was partitioned between water and EtOAc (300 ml each) The organic layer was dried evaporated in vacuo the residue was purified by flash column chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of NaOEt (from 3.63 gms Na) in ethanol (500 ml) was added 2,3-dichlorophenylacetonitrile (Example 14.3) in ethanol (150 ml). Ethyl formate (16.67 gms) was then added and the mixture stirred at 80° C. for 45 minutes, before adding a further quantity of ethyl formate (2.78 gms). After stirring at 80° C. for a further 1.5 hours, the precipitate was filtered off and dried in vacuo. The solid was dissolved in water, filtered, acidified with concentrated hydrochloric acid and the precipitate filtered off and dried in vacuo, 14.35 gms, 45% yield. After stirring at 80° C. for a further 1.5 hours the precipitate was filtered off dried in vacuo The solid was dissolved in water filtered the precipitate filtered off dried in vacuo, 14.35 gms, 45% yield

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of NaOEt (from 3.63 gms Na) in ethanol (500 ml) was added 2,3-dichlorophenylacetonitrile (Example 14.3) in ethanol (150 ml). Ethyl formate (16.67 gms) was then added and the mixture stirred at 80° C. for 45 minutes, before adding a further quantity of ethyl formate (2.78 gms). After stirring at 80° C. for a further 1.5 hours, the precipitate was filtered off and dried in vacuo. The solid was dissolved in water, filtered, acidified with concentrated hydrochloric acid and the precipitate filtered off and dried in vacuo, 14.35 gms, 45% yield. After stirring at 80° C. for a further 1.5 hours the precipitate was filtered off dried in vacuo The solid was dissolved in water filtered the precipitate filtered off dried in vacuo, 14.35 gms, 45% yield