pyrrolidine;hydrochloride

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

Procedure: A mixture of 1-(2,3-dimethylphenyl)-1-propanone (11.2 g), paraformaldehyde (2.70 g), pyrrolidine-hydrochloride (9.7g), and hydrochloric acid (0.5 ml) in isopropyl alcohol (15 ml) was refluxed for 8.5 hours. The reaction mixture was evaporated in vacuo to give the residue. The residue was dissolved in water and then washed with ethyl acetate. The aqueous layer was extracted with dichloromethane and then dried over anhydrous magnesium sulfate. The mixture was filtered and then the filtrate was evaporated in vacuo to give the residue. The residue was recrystallized from CH2Cl2 - AcOEt to give 2-methyl-1-(2,3-dimethylphenyl)-3-pyrrolidino-1-propanone hydrochloride (13.1 g, Y: 64.7%) as colorless prisms, m.p. 149°-151° C. IR ν (the free base)maxneat : 1690 cm-1 ##STR323## was refluxed for 8.5 hours The reaction mixture was evaporated in vacuo to give the residue washed with ethyl acetate The aqueous layer was extracted with dichloromethane dried over anhydrous magnesium sulfate The mixture was filtered the filtrate was evaporated in vacuo to give the residue The residue was recrystallized from CH2Cl2 - AcOEt

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

Procedure: A mixture of 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-1-propanone (4.37g), paraformaldehyde (1.80g), pyrrolidine hydrochloride (3.23g), and hydrochloric acid (0.2 ml) in isopropyl alcohol (50 ml) was refluxed for 8 hours. The reaction mixture was evaporated in vacuo to give the residue. The residue was partitioned into water and ethyl ether. The aqueous layer was extracted, neutralized with ammonia water, and then extracted with ethyl ether. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated in vacuo to give 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-2-methyl-3-pyrrolidino -1-propanone. (5.06; yield: 83.9%). was refluxed for 8 hours The reaction mixture was evaporated in vacuo to give the residue The residue was partitioned into water and ethyl ether The aqueous layer was extracted extracted with ethyl ether The organic layer was dried over anhydrous magnesium sulfate filtered The filtrate was evaporated in vacuo

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

Procedure: A mixture of 1-(4-trifluoromethylphenyl)-1-propanone (2.50g), paraformaldehyde (1.10g), pyrrolidine hydrochloride (1.60g), and hydrochloric acid (0.1 ml) was refluxed for 16 hours. The mixture was evaporated in vacuo to give the residue. The residue was partitioned into water and ethyl acetate. The aqueous layer was neutralized with ammonia water and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated in vaccuo to give 1-(4-trifluoromethylphenyl)-2-methyl-3-pyrrolidino-1propanone (1.58g; yield: 44.8%) as an oil. was refluxed for 16 hours The mixture was evaporated in vacuo to give the residue The residue was partitioned into water and ethyl acetate extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered The filtrate was evaporated in vaccuo

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

Procedure: A mixture of 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-1-butanone (2.50g), paraformaldehyde (0.42g), pyrrolidine hydrochloride (1.51g), and hydrochloric acid (0.2 ml) in isopropyl alcohol (7 ml) was refluxed for 15 hrs. The reaction mixture was evaporated in vacuo to give the residue. The residue was partitioned into water and ethyl ether. The aqueous layer, was extracted, neutralized with ammonia water, and then extracted with ethyl ether. The organic layer was dried over anhydrous magnesium sulfate. The mixture was filtered and the filtrate was evaporated in vacuo to give 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-2-ethyl-3-pyrrolidino-1-propanone (2.13 g, Yield: 62.8 %) as an oil. was refluxed for 15 hrs The reaction mixture was evaporated in vacuo to give the residue The residue was partitioned into water and ethyl ether The aqueous layer, was extracted extracted with ethyl ether The organic layer was dried over anhydrous magnesium sulfate The mixture was filtered the filtrate was evaporated in vacuo

Conditions: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (±)-trans-2-chloro-6-propyl-5,5a,6,7,8,9,9a,10-octahydropyrido[2,3-g]quinoline hydrochloride (2.50 g, 8.3 mmol) and pyrrolidine hydrochloride (10 g) was heated to 210° C. to form a homogeneous molten semi-solid. After 45 minutes the molten semi-solid was poured into water, made basic with dilute NaOH solution, and extracted with methylene chloride. The extract was dried (Na2SO4) and concentrated to give the crude product as a brown solid. Purification by flash chromatography (10% methanol in methylene chloride, NH4OH) provided (±)-trans-2-pyrrolidino-6-propyl-5,5a, 6,7,8,9,9a,10-octahydropyrido[2,3-g]quinoline (Rf=0.45, 1.32 g, 53% yield) as a brown oil. NMR (90 MHz, CDCl3): 7.03 (doublet, J=8 Hz, 1H), 6.07 (doublet, J=8 Hz, 1H), 3.55-3.11 (multiplet, 4H), 3.11-1.00 (multiplet, 20H), 0.89 (triplet, J=7 Hz, 3H). to form a homogeneous molten semi-solid extracted with methylene chloride The extract was dried (Na2SO4) concentrated to give the crude product as a brown solid Purification by flash chromatography (10% methanol in methylene chloride, NH4OH)

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

Procedure: A mixture of 1-(2,3-dimethylphenyl)-1-propanone (11.2 g), paraformaldehyde (2.70 g), pyrrolidine-hydrochloride (9.7 g), and hydrochloric acid (0.5 ml) in isopropyl alcohol (15 ml) was refluxed for 8.5 hours. The reaction mixture was evaporated in vacuo to give the residue. The residue was dissolved in water and then washed with ethyl acetate. The aqueous layer was extracted with dichloromethane and then dried over anhydrous magnesium sulfate. The mixture was filtered and then the filtrate was evaporated in vacuo to give the residue. The residue was recrystallized from CH2Cl2 --AcOEt to give 2-methyl-1-(2,3-dimethylphenyl)-3-pyrrolidino-1-propanone hydrochloride (13.1 g, Y: 64.7%) as colorless prisms, m.p. 149°-151° C. ##STR319## was refluxed for 8.5 hours The reaction mixture was evaporated in vacuo to give the residue washed with ethyl acetate The aqueous layer was extracted with dichloromethane dried over anhydrous magnesium sulfate The mixture was filtered the filtrate was evaporated in vacuo to give the residue The residue was recrystallized from CH2Cl2

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

Procedure: A mixture of 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-1-propanone (4.37 g), paraformaldehyde (1.80 g), pyrrolidine hydrochloride (3.23 g), and hydrochloric acid (0.2 ml) in isopropyl alcohol (50 ml) was refluxed for 8 hours. The reaction mixture was evaporated in vacuo to give the residue. The residue was partitioned into water and ethyl ether. The aqueous layer was extracted, neutralized with ammonia water, and then extracted with ethyl ether. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated in vacuo to give 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-2-methyl-3-pyrrolidino-1-propanone. (5.06; yield: 83.9%). ##STR318## was refluxed for 8 hours The reaction mixture was evaporated in vacuo to give the residue The residue was partitioned into water and ethyl ether The aqueous layer was extracted extracted with ethyl ether The organic layer was dried over anhydrous magnesium sulfate filtered The filtrate was evaporated in vacuo

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

Procedure: A mixture of 1-(4-trifluoromethylphenyl)-1-propanone (2.50 g), paraformaldehyde (1.10 g), pyrrolidine hydrochloride (1.60 g), and hydrochloric acid (0.1 ml) was refluxed for 16 hours. The mixture was evaporated in vacuo to give the residue. The residue was partitioned into water and ethyl acetate. The aqueous layer was neutralized with ammonia water and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated in vaccuo to give 1-(4-trifluoromethylphenyl)-2-methyl-3-pyrrolidino-1-propanone (1.58 g; yield: 44.8%) as an oil. ##STR317## 7.70 (2H, d, J=8.0 Hz, aromatic H), 8.05 (2H, d, J=8.0 Hz, aromatic H). was refluxed for 16 hours The mixture was evaporated in vacuo to give the residue The residue was partitioned into water and ethyl acetate extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered The filtrate was evaporated in vaccuo

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

Procedure: A mixture of 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-1-butanone (2.50 g), paraformaldehyde (0.42 g), pyrrolidine hydrochloride (1.51 g), and hydrochloric acid (0.2 ml) in isopropyl alcohol (7 ml) was refluxed for 15 hours. The reaction mixture was evaporated in vacuo to give the residue. The residue was partitioned into water and ethyl ether. The aqueous layer, was extracted, neutralized with ammonia water, and then extracted with ethyl ether. The organic layer was dried over anhydrous magnesium sulfate. The mixture was filtered and the filtrate was evaporated in vacuo to give 1-(4-methoxy-5,6,7,8-tetrahydro-1-naphthyl)-2-ethyl-3-pyrrolidino-1-propanone (2.13 g, Yield: 62.8%) as an oil. ##STR186## was refluxed for 15 hours The reaction mixture was evaporated in vacuo to give the residue The residue was partitioned into water and ethyl ether The aqueous layer, was extracted extracted with ethyl ether The organic layer was dried over anhydrous magnesium sulfate The mixture was filtered the filtrate was evaporated in vacuo

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

Procedure: A solution of 5.10 g of 4'-cyclohexylpropiophenone in 15 ml of ethyl acetate, 2.50 g of pyrrolidine hydrochloride, 1.30 g of paraformaldehyde and 0.5 ml of 22% hydrogen chloride-ethyl acetate were treated in the same manner as that described for Example 3 to give 3.65 g of hydrochloride of the desired compound, which were recrystallized from a mixture of ethanol and ether as colorless needles, mp 186°-187°.

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

Procedure: A solution of 5.10 g of 4'-cyclohexylpropiophenone in 15 ml of ethyl acetate, 2.50 g of pyrrolidine hydrochloride, 1.30 g of paraformaldehyde and 0.5 ml of 22% hydrogen chloride-ethyl acetate were treated in the same manner as that described for Example 3 to give 3.65 g of hydrochloride of the desired compound, which were recrystallized from a mixture of ethanol and ether as colorless needles, mp 186°-187°.

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

Procedure: A solution of 5.40 g of 4'-isobutylpropiophenone in 15 ml of ethyl acetate, 3.00 g of pyrrolidine hydrochloride, 1.30 g of paraformaldehyde and 0.5 ml of 22% hydrogen chloride-ethyl acetate were treated in the same manner as that described for Example 3 to give 3.53 g of hydrochloride of the desired compound which were recrystallized from methyl ethyl ketone as colorless scales, mp 127°-128°.