(Z)-1,3-dichloroprop-1-ene

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:

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: Ethyl 3-methylpyrazole-4-carboxylate (5.0 g) was added to sodium alcoholate prepared from 0.75 g of metallic sodium and 30 ml of ethanol. To the homogeneous mixture was added 3.6 g of 1,3-dichloropropene, and the mixture was refluxed for 2 hours. After the reaction, the reaction mixture was discharged into water and extracted with ethyl acetate. The extract was chromatographed on a silica gel column, and the column was eluted with hexane/ethyl acetate to give 2.5 g (34%) of a Z isomer of ethyl 1-(gamma-chloroallyl)-3-methylpyrazole-4-carboxylate and 1.5 g (20 %) of its E isomer. The Z isomer (2.5 g) was stirred under heat for 4 hours together with a mixture of 25 ml of ethanol, 2.5 g of sodium hydroxide and 25 ml of water. After the reaction, the reaction mixture was cooled to room temperature, and with cooling, concentrated hydrochloric acid was added to adjust its pH to 4 to 5. The precipitated crystals were collected by filtration and dried. Recrystallization from water gave 0.3 g (yield 14%) of the Z isomer of 1-(gamma-chloroallyl)-3-methylpyrazole-4-carboxylic acid. m.p. 96°-100° C. the mixture was refluxed for 2 hours After the reaction extracted with ethyl acetate The extract was chromatographed on a silica gel column the column was eluted with hexane/ethyl acetate

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

Procedure: Potassium carbonate (161.2 g) and potassium iodide (5 g) were added to a solution of (R)-1(1-naphthyl)ethylamine (100 g) and 1,3-dichloropropene (97.3 g) in acetonitrile (1 L) at room temperature. The reaction mixture was refluxed at 80° C. to 85° C. for 4 hours. After the completion of the reaction, the mixture was cooled to room temperature and de-ionized water (500 mL) was added. The solution was stirred for 15 minutes and layers were separated. The organic layer was concentrated under vacuum at 55° C. to 60° C. till about 100 to 150 mL of residue was left. Toluene (500 mL) was added to the residue and the organic layer was washed twice with de-ionized water (2×250 mL). The organic layer was concentrated under vacuum at 55° C. to 60° C. Isopropyl alcohol was added to the residue and stirred for 10 minutes at room temperature. The pH of the solution was adjusted to 0.5 to 1.0 using concentrated hydrochloric acid (35 mL) and stirred for one hour at room temperature. The solid was filtered, washed with isopropyl alcohol (2×100 mL) and dried under vacuum at 45° C. to 50° C. The reaction mixture was refluxed at 80° C. to 85° C. for 4 hours After the completion of the reaction layers were separated The organic layer was concentrated under vacuum at 55° C. to 60° C. till about 100 to 150 mL of residue was left Toluene (500 mL) was added to the residue the organic layer was washed twice with de-ionized water (2×250 mL) The organic layer was concentrated under vacuum at 55° C. to 60° C Isopropyl alcohol was added to the residue stirred for 10 minutes at room temperature stirred for one hour at room temperature The solid was filtered washed with isopropyl alcohol (2×100 mL) dried under vacuum at 45° C. to 50° C.

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

Procedure: Potassium carbonate (161.2 g) and potassium iodide (5 g) were added to the mixture of 1,3-dichloropropene (97.3 g) and (R)-1-(1-naphthyl)ethylamine (100 g) in isopropyl alcohol (500 mL) at room temperature. The reaction mixture was refluxed at 80° C. to 85° C. for about 4 hours. After the completion of the reaction, mixture was cooled to room temperature and filtered through hyflo bed. Hyflo bed was washed with isopropyl alcohol (500 mL). The filtrate was combined and treated with hydrochloric acid (6 Normal; 100 mL) at room temperature. The solution was allowed to stir for about one hour at room temperature to give solid. The solid was filtered and was washed twice with isopropyl alcohol (2×100 mL). Methanol (750 mL) was added to the wet solid and stirred for 10-15 minutes at room temperature. The pH of solution was adjusted to 11 to 12 using a solution of sodium hydroxide in water (20%). The solution was diluted with de-ionized water (750 mL) and extracted with dichloromethane (500 mL). Layers were separated and the organic layer was washed twice with de-ionized water (2×500 mL). The organic layer was completely concentrated under vacuum at 40° C. to 45° C. to give 3-chloro-N-[(1R)-1-(naphthalen-1-yl)ethyl]prop-2-en-1-amine as oil. The reaction mixture was refluxed at 80° C. to 85° C. for about 4 hours After the completion of the reaction, mixture filtered through hyflo bed Hyflo bed was washed with isopropyl alcohol (500 mL) treated with hydrochloric acid (6 Normal; 100 mL) at room temperature to give solid The solid was filtered was washed twice with isopropyl alcohol (2×100 mL) Methanol (750 mL) was added to the wet solid stirred for 10-15 minutes at room temperature The solution was diluted with de-ionized water (750 mL) extracted with dichloromethane (500 mL) Layers were separated the organic layer was washed twice with de-ionized water (2×500 mL) The organic layer was completely concentrated under vacuum at 40° C. to 45° C.

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.2 (350 mg, 1.29 mmol) in DMF (7 ml) was cooled to 0° C. and NaH (93 mg, 3.85 mmol) was added. The resulting mixture was stirred for 15 mins and 1,3 dichloropropene (358 μl, 3.85 mmol) was added. The mixture was allowed to warm to 25 ° C. and stirred for 15 h. The mixture was then concentrated. H2O (10 ml) was added to the residue and the solution was extracted with EtOAc (3×10 ml). The combined organic layers were dried with MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc/Hex 1:9) to afford 3.3 (400 mg, 89%) as a pale yellow oil. FABMS (NBA/NaI) 346 (M+H+ expected 346). stirred for 15 h The mixture was then concentrated H2O (10 ml) was added to the residue the solution was extracted with EtOAc (3×10 ml) The combined organic layers were dried with MgSO4 concentrated The residue was purified by flash chromatography (SiO2, EtOAc/Hex 1:9)

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

Procedure: A solution of 250 g of N-cinnamyltrifluoroacetamide in 1 liter of hexamethylphosphoric acid triamide (HMPT) is added dropwise with ice-cooling and stirring under a nitrogen atmosphere, to a suspension of 27 g of sodium hydride in 400 ml of HMPT. After the evolution of gas has ceased, a solution of 130 g of 1,3-dichloropropene and 1 g of sodium iodide in 1 liter of HMPT is added dropwise and the mixture stirred for 16 hours at room temperature. The reaction mixture is then poured on to water and extracted with ether. The ethereal solution is dried over sodium sulphate, evaporated and the oily residue chromatographed on 3.5 kg of silica gel with toluene to yield N-(3-chloro-2-propenyl)-N-cinnamyl-trifluoroacetamide as an oil. cooling extracted with ether The ethereal solution is dried over sodium sulphate evaporated the oily residue chromatographed on 3.5 kg of silica gel with toluene