6-氯己酰氯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1,8 dichloro-3-octanone: A well stirred, ice-cooled solution of 30.35 g (179.6 mmol) of 6-chlorohexanoyl chloride in 300 ml of dry CCl4 was degassed with nitrogen for 1/2 hr. AlCl3 (26.34 g, 179.6 mmol) was added in portions, then ethylene was bubbled in at a rate so that no excess ethylene escaped from the reaction vessel. Ethylene was allowed to bubble through the reaction mixture at 0° C. for 2 hrs. and at ambient temperature overnight. The reaction mixture was poured into 800 ml ice-water and extracted with chloroform (2×400 ml). The combined chloroform extracted were washed with sat'd aq. NaHCO3 (500 ml), H2O (500 ml), sat'd NaCl (500 ml) and dried over MgSO4. After the removal of the solvent, 15.2 g (43%) of crude 1,8-dichlorooctanone was obtained, which was used without further purification. NMR(CDCl3): δ1.44 (6H, m, --CH2 --), δ2.34 (2H, t, ##STR19## J=3.0 Hz), δ2.85 (2H, t, ##STR20## J=3.0 Hz), δ3.52 (2H, t, --CH2Cl, J=3 Hz) δ3.74 (2H, t, --CH2Cl, J=3.0 Hz). was degassed with nitrogen for 1/2 hr ethylene was bubbled in at a rate so that no excess ethylene to bubble through the reaction mixture at 0° C. for 2 hrs at ambient temperature overnight The reaction mixture was poured into 800 ml ice-water extracted with chloroform (2×400 ml) The combined chloroform extracted were washed with sat'd aq. NaHCO3 (500 ml), H2O (500 ml), sat'd NaCl (500 ml) dried over MgSO4 After the removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1,8 dichloro-3-octanone: A well stirred, ice-cooled solution of 30.35 g (179.6 mmol) of 6-chlorohexanoyl chloride in 300 ml of dry CCl4 was degassed with nitrogen for 1/2 hr. AlCl3 (26.34 g, 179.6 mmol) was added in portions, then ethylene was bubbled in at a rate so that no excess ethylene escaped from the reaction vessel. Ethylene was allowed to bubble through the reaction mixture at 0° C. for 2 hrs. and at ambient temperature overnight. The reaction mixture was poured into 800 ml ice-water and extracted with chloroform (2×400 ml). The combined chloroform extracted were washed with sat'd aq. NaHCO3 (500 ml), H2O (500 ml), sat'd NaCl (500 ml) and dried over MgSO4. After the removal of the solvent, 15.2 g (43%) of crude 1,8-dichlorooctanone was obtained, which was used without further purification. NMR(CDCl3): δ1.44 (6H, m, --CH2 --), δ2.34 (2H, t, ##STR19## J=3.0 Hz), δ2.85 (2H, t, ##STR20## J=3.0 Hz), δ3.52 (2H, t, --CH2Cl, J=3 Hz) δ3.74 (2H, t, --CH2Cl, J=3.0 Hz). was degassed with nitrogen for 1/2 hr ethylene was bubbled in at a rate so that no excess ethylene to bubble through the reaction mixture at 0° C. for 2 hrs at ambient temperature overnight The reaction mixture was poured into 800 ml ice-water extracted with chloroform (2×400 ml) The combined chloroform extracted were washed with sat'd aq. NaHCO3 (500 ml), H2O (500 ml), sat'd NaCl (500 ml) dried over MgSO4 After the removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1,8 dichloro-3-octanone: A well stirred, ice-cooled solution of 30.35 g (179.6 mmol) of 6-chlorohexanoyl chloride in 300 ml of dry CCl4 was degassed with nitrogen for 1/2 hr. AlCl3 (26.34 g, 179.6 mmol) was added in portions, then ethylene was bubbled in at a rate so that no excess ethylene escaped from the reaction vessel. Ethylene was allowed to bubble through the reaction mixture at 0° C. for 2 hrs. and at ambient temperature overnight. The reaction mixture was poured into 800 ml ice-water and extracted with chloroform (2×400 ml). The combined chloroform extracted were washed with sat'd aq. NaHCO3 (500 ml), H2O (500 ml), sat'd NaCl (500 ml) and dried over MgSO4. After the removal of the solvent, 15.2 g (43%) of crude 1,8-dichlorooctanone was obtained, which was used without further purification. NMR(CDCl3): δ1.44 (6H, m, --CH2 --), δ2.34 (2H, t, ##STR19## J=3.0 Hz), δ2.85 (2H, t, ##STR20## J=3.0 Hz), δ3.52 (2H, t, --CH2Cl, J=3 Hz) δ3.74 (2H, t, --CH2Cl, J=3.0 Hz). was degassed with nitrogen for 1/2 hr ethylene was bubbled in at a rate so that no excess ethylene to bubble through the reaction mixture at 0° C. for 2 hrs at ambient temperature overnight The reaction mixture was poured into 800 ml ice-water extracted with chloroform (2×400 ml) The combined chloroform extracted were washed with sat'd aq. NaHCO3 (500 ml), H2O (500 ml), sat'd NaCl (500 ml) dried over MgSO4 After the removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 456 parts of 6-caprolactone and 9 parts of N,N-dimethylpiperidinium chloride are initially taken in the stirred reactor described in Example 1. 380 parts of phosgene and 70 parts of hydrogen chloride are passed in at 170°-175° C. in the course of 7 hours. The reaction mixture is then kept at this temperature for a further hour. Any phosgene and hydrogen chloride still present are blown out with nitrogen, and the reaction mixture is then worked up by distillation under reduced pressure. 424 parts of 6-chlorohexanoyl chloride and 86 parts of caprolactone are obtained. The conversion is 81% and the yield is 77.3%, based on lactone used. are passed in at 170°-175° C. in the course of 7 hours The reaction mixture is then kept at this temperature for a further hour the reaction mixture is then worked up by distillation under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 456 parts of 6-caprolactone and 9 parts of N,N-dimethylpiperidinium chloride are initially taken in the stirred reactor described in Example 1. 380 parts of phosgene and 70 parts of hydrogen chloride are passed in at 170°-175° C. in the course of 7 hours. The reaction mixture is then kept at this temperature for a further hour. Any phosgene and hydrogen chloride still present are blown out with nitrogen, and the reaction mixture is then worked up by distillation under reduced pressure. 424 parts of 6-chlorohexanoyl chloride and 86 parts of caprolactone are obtained. The conversion is 81% and the yield is 77.3%, based on lactone used. are passed in at 170°-175° C. in the course of 7 hours The reaction mixture is then kept at this temperature for a further hour the reaction mixture is then worked up by distillation under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This compound was prepared from [3,3-bis(ethyloxy)propyl]amine and 6-chlorohexanoyl chloride using methods similar to Example 669: step 1 to provide a yellow viscous oil: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.10 (t, J=7.09 Hz, 6 H), 1.28-1.40 (m, 2 H), 1.44-1.56 (m, 2 H), 1.59-1.75 (m, 4 H), 2.04 (t, J=7.23 Hz, 2 H), 3.01-3.09 (m, 2 H), 3.41 (dq, J=9.55, 7.07 Hz, 2 H), 3.50-3.64 (m, 4 H), 4.48 (t, J=5.69 Hz, 1 H), 7.74 (t, J=5.33 Hz, 1 H); ES+ MS: 302 (M+Na+). to provide a yellow viscous oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-(4-fluorophenyl)ethanamine 15b (5.0 g, 35.9 mmol) in a mixture of 10 mL of DCM and 14.5 mL of pyridine, with ice cooling, was added dropwise a solution of 6-chlorohexanoyl chloride 15a in 20 mL of DCM. After the addition was compete, cooling was removed and the resulting precipitate was stirred overnight. The reaction mixture was diluted with 100 mL of ther and washed with 100 mL of 1M HCl. The organic phase was dried over MgSO4 and concentrated to furnish 9.2 g of crude 5-chloro-N-(1-(4-fluorophenyl)ethyl)pentanamide 15c which was used in the next step without purification. After the addition cooling was removed The reaction mixture was diluted with 100 mL of ther and washed with 100 mL of 1M HCl The organic phase was dried over MgSO4 concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5,11-dihydro-6H-pyrido-[2,3-b][1,4]-benzodiazepine-6-one and 6-chloro-caproyl chloride in xylene was reacted to obtain 11-(6-chloro-caproyl)-5,11-dihydro-6H-pyrido-[2,3-b][1,4]-benzodiazepine-6-one melting at 128°-130° C.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Aluminum chloride (16 g, 0.12 mol) is suspended in carbon tetrachloride (80 ml) and 6-chlorohexanoyl chloride (20 g, 0.12 mol) is added dropwise to the suspension with ice-cooling. After completion of addition, the mixture is stirred for 15 minutes and benzene (7.8 g, 0.1 mol) is added dropwise to the mixture with ice-cooling. After stirring with ice-cooling for 1 hour, the mixture is poured into ice-hydrochloric acid and extracted with carbon tetrachloride. The carbon tetrachloride extract is washed with water, saturated aqueous sodium bicarbonate, water and then saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The dried solution is distilled to obtain 5-chloropentyl phenyl ketone (7.3 g), b.p. 143°-150° C./0.5 mmHg. cooling After completion of addition cooling After stirring with ice- cooling for 1 hour extracted with carbon tetrachloride The carbon tetrachloride extract is washed with water, saturated aqueous sodium bicarbonate, water saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate The dried solution is distilled

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Reaction under N2 atmosphere. BF3 in diethylether (215 ml) was cooled to 0° C. 3-Fluoro-phenol (0.25 mol) was added. 6-Chloro-hexanoyl chloride (0.51 mol) added and the resulting reaction mixture was stirred for 15 min at 0° C., then allowed to warm to room temperature. The reaction mixture was then stirred overnight at 130° C. The mixture was cooled room temperature. Water was added while cooling. This mixture was extracted twice with diisopropyl ether. The separated organic layer was dried, filtered and the solvent evaporated. The residue was by column chromatography over silica gel (eluent: CH2Cl2/hexane 50/50), then by HPLC (eluent: CH2Cl2/hexane 50/50). The fractions were collected and the solvent was evaporated, yielding 52.2 g of 6-chloro-1-(4-fluoro-2-hydroxyphenyl)-1-hexanone (interm 17). Reaction under N2 atmosphere the resulting reaction mixture to warm to room temperature The reaction mixture was then stirred overnight at 130° C The mixture was cooled room temperature while cooling This mixture was extracted twice with diisopropyl ether The separated organic layer was dried filtered the solvent evaporated The fractions were collected the solvent was evaporated