hex-5-enoic acid

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 5-hexenoic acid q-1 (6.00 g, 52.6 mmol), t-butyl alcohol (72.2 mL, 735.84 mmol) and DMAP (1.28 g, 10.51 mmol) in DCM (150 mL) at −10° C. was added DCC (16.26 g, 78.84 mmol). After stirring at room temperature overnight, solid was filtered off. The filtrate was evaporated under reduced pressure to give a crude oil, which was purified by chromatography (Biotage; 65i). Elution with a gradient of EtOAc/Hexane from 5/95 to 10/90 yielded 4.16 g (46.53%) of t-butyl ester q-2, which displayed a 1H NMR spectrum that matched literature (Johnson, P. Y.; Berchtold, G. A. J. Org. Chem. 1970, 35, 584-592) and was used without further purification). solid was filtered off The filtrate was evaporated under reduced pressure to give a crude oil, which was purified by chromatography (Biotage; 65i) Elution with a gradient of EtOAc/Hexane from 5/95 to 10/90

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: FIG. 6 shows an alternative synthesis of 5-decenyl acetate, in which 1-hexene is reacted with 5-hexenoic acid in the presence of Grubbs' catalyst to produce 5-decenoic acid that can be recrystallized, reduced to an alcohol, and acetylated to yield a greater than 90% E-5-decenyl acetate.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Hexenoic acid (4.9 g, 42.9 mmol) was refluxed in 80 ml of methanol with catalytic p toluene sulfonic acid monohydrate for 40 hours. The solution was cooled and concentrated then poured into ether/water. The ether layer was dried over sodium sulfate and concentrated to give 4.6 g (35.9 mmol), 84% of the title compound. The solution was cooled concentrated then poured into ether/water The ether layer was dried over sodium sulfate concentrated

反応条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Via Lactone XXXVII. Refer to Chart 3. A phosphonate reagent is first prepared. Methyl 5-hexenoate is prepared from 5-hexenoic acid by reaction with methanol and concentrated sulfuric acid in refluxing ethylene dichloride, thereafter washing and distilling the product. The anion of dimethyl methylphosphonate, prepared from dimethyl methylphosphonate (82 g.) and 400 ml. of 1.6 M butyllithium in 800 ml. of tetrahydrofuran at -55° to -60° C. is treated with methyl 5-hexenoate (41 g.) added in 65 ml. of tetrahydrofuran over about 10 min. The mixture is stirred at -75° C. for 2 hr. and then at about 25° C. for 18 hr. Acetic acid (26 ml.) is added and the solvent removed under reduced pressure. The residue is taken up in water and ether-methylene chloride (3:1). The organic phase, combined with extractions of the aqueous phase, is washed with cold aqueous sodium bicarbonate and brine, dried, and concentrated. There is obtained, on distillation, dimethyl 2-oxo-6-heptenylphosphonate. washing distilling the product The anion of dimethyl methylphosphonate, prepared from dimethyl methylphosphonate (82 g.) and 400 ml added in 65 ml and then at about 25° C. for 18 hr the solvent removed under reduced pressure The organic phase, combined with extractions of the aqueous phase is washed with cold aqueous sodium bicarbonate and brine dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cholesterol (2.0 g, 5.17 mM) in methylene chloride (20 mL) was added 5-hexenoic acid (0.68 mL, 5.69 mM) followed by the addition of DCC (1.60 g, 7.76 mM) and 4-PP (0.115 g, 0.78 mM) under nitrogen atmosphere. The resulting reaction mixture was stirred at ambient temperature for 1 h and worked up with the addition of methyl t-butyl ether (60 mL). The urea was filtered off, and the product was transferred to a separatory funnel, washed with 1N HCl (10 mL), water (30 mL) and brine (30 mL). The product was filtered after drying over MgSO4 and the solvent was evaporated to leave a residue. The product obtained in >95% yield was characterized by 1H NMR. The resulting reaction mixture The urea was filtered off the product was transferred to a separatory funnel washed with 1N HCl (10 mL), water (30 mL) and brine (30 mL) The product was filtered after drying over MgSO4 the solvent was evaporated to leave a residue The product obtained in >95% yield

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Hex-5-enoic acid methyl ester was prepared as follows. Hex-5-enoic acid (2.00 g, 17.5 mmol) was dissolved in diethyl ether (8 mL) and methanol (4 mL) and cooled to 0° C. To this solution was added 2.0 M Trimethylsilyl diazomethane (9 mL) dropwise. It was noted that a yellow TMS-diazomethane solution dissipates upon stirring with the reaction mixture, and the reaction is deemed complete when the yellow color persists. Caution should be observed, as the reaction is associated with vigorous gas evolution. When the yellow color persists in the reaction mixture, TLC analysis was conducted and confirmed consumption of the acid. The solvent was evaporated under reduced pressure carefully (product is somewhat volatile) and replaced with ethyl acetate. The solution was washed with saturated NaHCO3, dried, and the filtrate was used directly in the next step. 1H NMR (400 MHz) CDCl3 δ 5.45 (m, 1H), δ 4.9 (m, 2H), δ 3.65 (s, 3H), δ 2.20 (t, 2H), δ 2.05 (m, 2H), δ 1.70 (m, 2H). consumption of the acid The solvent was evaporated under reduced pressure carefully (product The solution was washed with saturated NaHCO3 dried

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 50 ml two-necked round-bottom flask was flame dried and allowed to be cooled under nitrogen. (1S,2R,3R,4R)-2-allyl-4-(tert-butyldimethylsilyloxy)-3-((R,E)-3-(triethylsilyloxy)-4-(3-(trifluoromethyl)phenoxy)but-1-enyl)cyclopentanol (1 g, 1.66 mmol) in 10 ml of DMF, 0.05 g (0.33 mmol) of DMAP, 0.21 g (1.83 mmol) of 5-hexenoic acid, and 0.41 g (2.00 mmol) of N,N′-dicyclohexylcarbodiimide were added to the reaction flask. The reaction mixture was heated at 40° C. for 24 hours. The reaction was quenched with 10 ml saturated aqueous sodium bicarbonate. The reaction mixture was phase separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off and organic solvent was evaporated off under vacuum. The crude product was purified by chromatography and then concentrated under reduced pressure to provide 1.05 g of the title compound (90.52% yield). A 50 ml two-necked round-bottom flask was flame dried to be cooled under nitrogen The reaction was quenched with 10 ml saturated aqueous sodium bicarbonate separated the aqueous layer was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solid was filtered off organic solvent was evaporated off under vacuum The crude product was purified by chromatography concentrated under reduced pressure

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 50 ml two-necked round-bottom flask was flame dried and allowed to be cooled under nitrogen. (1S,2R,3R,4R)-2-allyl-4-(tert-butyldimethylsilyloxy)-3-((R,E)-3-(triethylsilyloxy)-4-(3-(trifluoromethyl)phenoxy)but-1-enyl)cyclopentanol (1 g, 1.66 mmol) in 10 ml of DMF, 0.05 g (0.33 mmol) of DMAP, 0.21 g (1.83 mmol) of 5-hexenoic acid, and 0.41 g (2.00 mmol) of N,N′-dicyclohexylcarbodiimide were added to the reaction flask. The reaction mixture was heated at 40° C. for 24 hours. The reaction was quenched with 10 ml saturated aqueous sodium bicarbonate. The reaction mixture was phase separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off and organic solvent was evaporated off under vacuum. The crude product was purified by chromatography and then concentrated under reduced pressure to provide 1.05 g of the title compound (90.52% yield). A 50 ml two-necked round-bottom flask was flame dried to be cooled under nitrogen The reaction was quenched with 10 ml saturated aqueous sodium bicarbonate separated the aqueous layer was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solid was filtered off organic solvent was evaporated off under vacuum The crude product was purified by chromatography concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Step EQ (1): Hex-5-enoic acid (240 mg, 2.1 mmol) and (2R,3S)-N1-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-5-methylhexane-1,3-diamine (1.1 g, 2.2 mmol, from Preparation BH) were coupled using a procedure analogous to Step CA (1) to afford N-((2R,3S)-1-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-ylamino)-2-(tert-butyldimethylsilyloxy)-5-methylhexan-3-yl)hex-5-enamide. LC-MS (M+H)+=587.47.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Step EQ (1): Hex-5-enoic acid (240 mg, 2.1 mmol) and (2R,3S)-N1-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-5-methylhexane-1,3-diamine (1.1 g, 2.2 mmol, from Preparation BH) were coupled using a procedure analogous to Step CA (1) to afford N-((2R,3S)-1-((1S,3R)-3-(allyloxy)-6-isopropoxy-2,3-dihydro-1H-inden-1-ylamino)-2-(tert-butyldimethylsilyloxy)-5-methylhexan-3-yl)hex-5-enamide. LC-MS (M+H)+=587.47.