1-chloroheptane

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

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by stirring. Further, 0.079 g (0.12 mmol) of tricyclohexylphosphonium tetra-para-tolylborate obtained in Example B-16 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.434 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by stirring. Further, 0.072 g (0.12 mmol) of tricyclohexylphosphonium tetraphenylborate obtained in Example A-4 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.435 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by stirring. Further, 0.079 g (0.12 mmol) of tricyclohexylphosphonium tetra-para-tolylborate obtained in Example B-16 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.434 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by stirring. Further, 0.072 g (0.12 mmol) of tricyclohexylphosphonium tetraphenylborate obtained in Example A-4 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.435 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by stirring. Further, 0.079 g (0.12 mmol) of tricyclohexylphosphonium tetra-para-tolylborate obtained in Example B-16 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.434 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by, stirring. Further, 0.072 g (0.12 mmol) of tricyclohexylphosphonium tetraphenylborate obtained in Example A-4 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.435 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: A soltuion of 3 g(19.4 mmol) of 5-chlorovaleryl chloride in 15 ml of anhydrous THF was added dropwise with vigorous stirring over 15 min. under nitrogen, to a solution of ethylmagnesium bromide (15 mL of 3M in ether) in 15 mL of anhydrous THF at -5° C. The reaction was allowed to warm up to room temperature and stirred for 2 hours. After cooling the mixture to 0° C. it was quenched with diluted hydrochloric acid. The mixture was extracted with ether, washed with water, dried over anh. MgSO4, filtered and evaporated. The residue was flash chromatographed through silicagel in CH2Cl2 to give 2.7 g (84%) of the chloroalcohol as a colorless liquid (5-hydroxy-5-ethyl-heptyl chloride). To a stirred solution of 1.32 g (10 mmol) of thiophenol and 1.32 g (11.3 mmol) of potassium tret.-butoxide was added 1.5 g (10 mmol) of the heptyl chloride as prepared above in 5 ml of anhydrous dimethyl formamide. The reaction mixture was stirred at room temperature overnight and extracted with dichloromethane. The organic layer was washed with 10% sodium carbonate solution and water and dried (MgSO4). Solvents were removed in vacuo and the crude oil was purified by silica gel chromatography with hexane-ethyl acetate to give the corresponding phenyl-sulfide (1.9 g) as a colorless oil. This sulfide was then dissolved in 30 mL of dry dichloromethane and 3.0 g (80-85%) of 3-chloroperbenzoic acid was added in portions with stirring and occasional cooling. The reaction mixture was stirred for 2 hrs, and quenched with 10% sodium bicarbonate. The combined organic extracts were washed with aqueous sodium sulfite and brine and dried (MgSO4). The solvents was removed in vacuo and the crude oil was purified by silica gel flash chromatography using hexane-ethyl acetate to afford the pure sulfone (1.4 g) as a colorless liquid. Calcd for C15H24O3S C, 63.34; H, 8.51; S, 11.27; Found: C,63.36; H, 8.61; S, 11.23. 1.0 g N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane was added to 560 mg of the above hydroxysulfone in 1 mL of anhydrous pyridine and the mixture stirred under nitrogen at 60° C. for 3 h. After evaporation of the pyridine under reduced pressure the crude product was flash chromatographed on a silica gel column with hexane followed by 9:1 hexane-ethyl acetate to give the pure hydroxy-protected sulfone (0.62 g). Calcd for C18H32O3SSI C, 60.62; H, 9.05; S 8.99 Found C, 60.73, H, 9.22; S, 8.88%, 1H NMR (CDCl3) δ 0.058 (9H,s,Si--(CH3)3) 3.07-3.12 (2H,m, 7-H) 7.57 (2H, t, J=6.8 Hz, Ar H metal) 7.65 (1 H,t, J=6.8 Hz, Ar H para) 7.92 (2H,d J=6.8 Hz,Ar H, Ortho). extracted with dichloromethane The organic layer was washed with 10% sodium carbonate solution and water dried (MgSO4) Solvents were removed in vacuo the crude oil was purified by silica gel chromatography with hexane-ethyl acetate

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by stirring. Further, 0.079 g (0.12 mmol) of tricyclohexylphosphonium tetra-para-tolylborate obtained in Example B-16 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.434 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: A 30-ml four-necked flask was equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser. 0.027 g (0.12 mmol) of palladium (II) acetate and 7 ml of N-methylpyrrolidinone were weighed in the flask, followed by, stirring. Further, 0.072 g (0.12 mmol) of tricyclohexylphosphonium tetraphenylborate obtained in Example A-4 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 25° C. for 30 minutes. 0.404 g (3 mmol) of n-heptyl chloride was added, followed by stirring at 25° C. for 30 minutes. 2 ml (4.4 mmol) of 2.2M tetrahydrofuran solution of phenylmagnesium chloride was added dropwise at 25° C. over a period of 10 minutes, followed by stirring at 25° C. for 19 hours. After the completion of the reaction, 6 ml of tetrahydrofuran and 10 ml of saturated aqueous ammonium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.435 g of 1-phenylheptane (yield: 82 mol % based on n-heptyl chloride). The identification of the product was made by mass spectroscopy. A 30-ml four-necked flask was equipped with a stirrer added into the flask The flask was purged with argon by stirring at 25° C. for 30 minutes by stirring at 25° C. for 30 minutes by stirring at 25° C. for 19 hours were added followed by separation The organic phase was purified by column chromatography

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

Procedure: 2-Pyrrolidineheptanoic acid is prepared from N-t-butoxycarbonylproline following steps A and B of Example 4 and step C of the procedure of Example 15. In step C, benzyl ω -chlorohexanoate is substituted for the 1-chloroheptane. The product thus obtained is hydrogenated in the presence of 10% palladium on charcoal and is then treated with trifluoroacetic acid, as in step E of the same procedure. The product thus obtained