洛索洛芬杂质49

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

实验步骤: A 2 liter round bottom flask, fitted with a mechanical stirrer, a reflux condenser and a thermometer, was charged with 412.4 g (2.75 mol) of 2-Cyclopentylidene-cyclopentanone and 500 ml methanol. The mixture was stirred until homogeneous at room temperature and then 40 g of sodium borohydride was added in small portions over a period of 1.5 hour. The reaction mixture was thereafter stirred for another 4 hours. During addition as well as thereafter the temperature was kept below 40° C. by cooling with a cold water bath if necessary. The reaction mixture was further stirred overnight. Thereafter it was quenched by dropwise addition, with stirring, of 250 ml of water. The aqueous and organic layers were separated and the aqueous layer extracted twice with 200 ml diethyl ether. The combined organic layers were washed with 200 ml water and dried over magnesium sulphate. After filtration the solvent was removed using a rotary evaporator and 444 g of crude product were obtained. This was fractioned under reduced pressure (0.4 kPa) through a 0.5 meter Sulzer-packed column. Fractions were collected at 90°-100° C. and odour assessed. The total of fractions with an acceptable odour was 182.9 g. The product could be further purified by recristallization from methanol. A 2 liter round bottom flask, fitted with a mechanical stirrer, a reflux condenser The reaction mixture was thereafter stirred for another 4 hours During addition as well as thereafter the temperature was kept below 40° C. by cooling with a cold water bath if necessary Thereafter it was quenched by dropwise addition with stirring, of 250 ml of water The aqueous and organic layers were separated the aqueous layer extracted twice with 200 ml diethyl ether The combined organic layers were washed with 200 ml water dried over magnesium sulphate After filtration the solvent was removed a rotary evaporator

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 1.90 g (41 mmole) of NaNH2 in 60 ml of dry toluene, 5.50 g (35 mmole) of 2-cyclopentylidene cyclopentanone was added dropwise below about 30° C. under stirring. The resulting mixture was stirred at about room temperature until no NH3 was evolved and then 3.8 g (32 mmole) of 2-dimethylaminoethyl chloride was added dropwise. The mixture was heated for about 2 hours at about 100° C. under stirring. On cooling, the mixture was acidified with 2N HCl. The aqueous layer was separated and the organic layer was extracted with 2N HCl. The combined aqueous layer was basified with 10% NaOH and extracted with ether. The ether extracts were dried over anhydrous MgSO4. The ether solution was treated with ethanolic hydrogen chloride to give 2-(1-cyclopenten-1-yl)-2-dimethylamino-ethyl cyclopentanone hydrochloride. was added dropwise below about 30° C. under stirring On cooling The aqueous layer was separated the organic layer was extracted with 2N HCl extracted with ether The ether extracts were dried over anhydrous MgSO4 The ether solution was treated with ethanolic hydrogen chloride

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

实验步骤: To a stirring solution of 2-cyclopentylidenecyclopentan-1-one (62.5 g, 0.417 moles) in dry THF (450 mL) at room temperature under nitrogen, was added NaH (60% oil dispersion, 20.0 g, 0.5 moles) in one portion. The mixture was stirred at room temperature for 30 min and then a solution of allyl chloride (38.3 g, 0.5 moles) in THF (100 mL) was added dropwise over 30 min. When the addition was complete, the reaction was warmed gently to approximately 40° C. It was determined by TLC and GC that the reaction was complete after 18 hours. Water was added to the reaction mixture and the layers were separated, with the organic layer being washed successively with 10% HCl (aqueous), saturated NaHCO3 (aqueous), and brine. The resulting organic layer was dried with MgSO4, filtered, and concentrated. The brown oil was distilled under vacuum to give 2-cyclopent-1-enyl-2-prop-2-enylcyclopentan-1-one (54.5 g, 69.0% yield). When the addition the reaction was warmed gently to approximately 40° C was complete after 18 hours the layers were separated, with the organic layer being washed successively with 10% HCl (aqueous), saturated NaHCO3 (aqueous), and brine The resulting organic layer was dried with MgSO4 filtered concentrated The brown oil was distilled under vacuum

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

实验步骤: To a stirring solution of cyclopentanone (336.5 g, 4.0 moles) in absolute ethanol (500 mL) at room temperature was added KOH (5.6 g, 0.1 mole) in one portion. The reaction was stirred at room temperature for 65 hours. The reaction was determined to be completed by TLC and GC analyses. Hexane was added to the reaction mixture and the layers were separated. The organic layer was washed successively with 10% HCl (aqueous), saturated NaHCO3 (aqueous) and brine. The resulting organic layer was dried with MgSO4, filtered, and concentrated. The brown oil was distilled under vacuum to give 2-cyclopentylidenecyclopentan-1-one (155 g, 52% yield). The structural formula of 2-cyclopentylidenecyclopentan-1-one is shown in FIG. 1. the layers were separated The organic layer was washed successively with 10% HCl (aqueous), saturated NaHCO3 (aqueous) and brine The resulting organic layer was dried with MgSO4 filtered concentrated The brown oil was distilled under vacuum

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 1.90 g (41 mmole) of NaNH2 in 60 ml of dry toluene, 5.50 g (35 mmole) of 2-cyclopentylidene cyclopentanone was added dropwise below about 30° C. under stirring. The resulting mixture was stirred at about room temperature until no NH3 was evolved and then 3.8 g (32 mmole) of 2-dimethylaminoethyl chloride was added dropwise. The mixture was heated for about 2 hours at about 100° C. under stirring. On cooling, the mixture was acidified with 2N HCl. The aqueous layer was separated and the organic layer was extracted with 2N HCl. The combined aqueous layer was basified with 10% NaOH and extracted with ether. The ether extracts were dried over anhydrous MgSO4. The ether solution was treated with ethanolic hydrogen chloride to give 2-(1-cyclopenten-1-yl)-2-dimethylamino-ethyl cyclopentanone hydrochloride. was added dropwise below about 30° C. under stirring On cooling The aqueous layer was separated the organic layer was extracted with 2N HCl extracted with ether The ether extracts were dried over anhydrous MgSO4 The ether solution was treated with ethanolic hydrogen chloride