3,5,5-trimethylhexanoyl chloride

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: A mixture of 143.4 grams of aluminum chloride and 351.6 grams of benzene was stirred at room temperature while 100 grams of 3,5,5-trimethylhexanoyl chloride was added to the reaction keeping the reaction temperature at approximately 35° C. over a period of 1.5 hours. The mixture was then stirred for 3 hours. The reaction mixture was poured into 500 grams of ice and stirred until all the ice dissolved. Water was added with cooling to give a homogenous mixture followed by extraction with 400 mL of ethyl acetate. The organic phase was washed with brine, dried with anhydrous magnesium sulfate and stripped to dryness to give 3,5,5-Trimethylhexanoylbenzene. was added to the reaction at approximately 35° C. of 1.5 hours dissolved with cooling to give a homogenous mixture followed by extraction with 400 mL of ethyl acetate The organic phase was washed with brine dried with anhydrous magnesium sulfate

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

実験手順: To a mixture of 143.3 grams of aluminum chloride and 400 mL of benzene was added 100 grams of 3,5,5-trimethylhexanoyl chloride over a 50 minute period at a rate such that the temperature did not exceed 35° C. When the addition was complete, the mixture was stirred at room temperature for three hours. The mixture was poured over 500 grams of ice and extracted with 400 mL of ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and the solvent was removed in vacuo to give 3,5,5-trimethylhexanoylbenzene. did not exceed 35° C When the addition extracted with 400 mL of ethyl acetate The organic phase was washed with brine dried over magnesium sulfate filtered the solvent was removed in vacuo

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

実験手順: Before the start of the reaction, the loop reactor is filled with a solution of 25.7% by weight of tert-butyl hydroperoxide and 15.0% by weight of potassium hydroxide in water. Initially 20.2 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 18.2 kg/h of a solution of 45% by weight of potassium hydroxide in water, 16.2 kg/h of water and 19.2 kg/h of 3,5,5-trimethylhexanoyl chloride are then fed to the loop reactor. Cooling with cooling water keeps the internal temperature at 25° C. in the loop reactor and in the stirred cell reactor. The partial neutralization is effected with 27.6 kg/h of 4% by weight hydrochloric acid at a temperature of 15° C. The organic phase is extracted with 23.6 kg/h of a 20% by weight aqueous solution of potassium hydroxide. This affords 26.2 kg/h of aqueous extract comprising 9.6% by weight of tert-butyl hydroperoxide and 18.0% by weight of potassium hydroxide, which are feeded into the loop reactor. From the time at which aqueous extract is recycled into the loop reactor, the metered addition of the feedstocks is changed to 16.6 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 7.8 kg/h of a solution of 45% by weight of potassium hydroxide in water and 4.8 kg/h of water. After the extraction, the organic phase is washed with 33.8 kg/h of a solution of 3% by weight of sodium sulphite and 1% by weight of sulphuric acid, and dried by stripping at 34° C. and 47 mbar. 24.6 kg/h of tert-butyl peroxy-3,5,5-trimethylhexanoate with a purity of 99.9% are obtained (98.2% yield based on 3,5,5-trimethylhexanoyl chloride). Before the start of the reaction at 25° C. The organic phase is extracted with 23.6 kg/h of a 20% by weight aqueous solution of potassium hydroxide This affords 26.2 kg/h of aqueous extract From the time at which aqueous extract the metered addition of the feedstocks After the extraction the organic phase is washed with 33.8 kg/h of a solution of 3% by weight of sodium sulphite and 1% by weight of sulphuric acid dried by stripping at 34° C.

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

実験手順: A mixture of 143.4 grams of aluminum chloride and 351.6 grams of benzene was stirred at room temperature while 100 grams of 3,5,5-trimethylhexanoyl chloride was added to the reaction keeping the reaction temperature at approximately 35° C. over a period of 1.5 hours. The mixture was then stirred for 3hours. The reaction mixture was poured into 500 grams of ice and stirred until all the ice dissolved. Water was added with cooling to give a homogenous mixture followed by extraction with 400 mL of ethyl acetate. The organic phase was washed with brine, dried with anhydrous magnesium sulfate and stripped to dryness to give 3,5,5-Trimethylhexanoylbenzene. was added to the reaction at approximately 35° C. of 1.5 hours dissolved with cooling to give a homogenous mixture followed by extraction with 400 mL of ethyl acetate The organic phase was washed with brine dried with anhydrous magnesium sulfate

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

実験手順: To a mixture of 143.3 grams of aluminum chloride and 400 mL of benzene was added 100 grams of 3,5,5-trimethylhexanoyl chloride over a 50 minute period at a rate such that the temperature did not exceed 35° C. When the addition was complete, the mixture was stirred at room temperature for three hours. The mixture was poured over 500 grams of ice and extracted with 400 mL of ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and the solvent was removed in vacuo to give 3,5,5-trimethylhexanoylbenzene. did not exceed 35° C When the addition extracted with 400 mL of ethyl acetate The organic phase was washed with brine dried over magnesium sulfate filtered the solvent was removed in vacuo

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

実験手順: To a mixture of 143.3 grams of aluminum chloride and 400 mL of benzene was added 100 grams of 3,5,5-trimethylhexanoyl chloride over a 50 minute period at a rate such that the temperature did not exceed 35° C. When the addition was complete, the mixture was stirred at room temperature for three hours. The mixture was poured over 500 grams of ice and extracted with 400 mL of ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and the solvent was removed in vacuo to give 3,5,5-trimethylhexanoylbenzene. did not exceed 35° C When the addition extracted with 400 mL of ethyl acetate The organic phase was washed with brine dried over magnesium sulfate filtered the solvent was removed in vacuo

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

実験手順: The reaction is effected in a reactor arrangement of a first reactor of type E with a downstream reactor of type C. Before the start of the reaction, the first reactor is filled with a solution of 25.6% by weight of tert-butyl hydroperoxide and 15.0% by weight of potassium hydroxide in water. 20.2 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 18.2 kg/h of a solution of 45% by weight of potassium hydroxide in water, 16.2 kg/h of water and 19.2 kg/h of 3,5,5-trimethylhexanoyl chloride are then fed to the first reactor. Cooling with cooling water keeps the internal temperature in the first reactor at 25° C. and in the second reactor at 25° C. The organic phase is removed from the reaction mixture withdrawn from the second reactor. The organic phase is washed successively with an 8% by weight solution of sodium hydroxide in water, with a solution of 10% by weight of sodium sulphite in water comprising acetic acid and with a 1% by weight solution of sodium hydrogen-carbonate in water, and then dried by stripping in a packed column at 34° C. and 47 mbar. 24.6 kg/h of tert-butyl peroxy-3,5,5-trimethylhexanoate are obtained (98.2% based on 3,5,5-trimethylhexanoyl chloride). The space-time yield is 1.98 kg/l·h. The reaction is effected in a reactor Before the start of the reaction at 25° C. at 25° C The organic phase is removed from the reaction mixture withdrawn from the second reactor The organic phase is washed successively with an 8% by weight solution of sodium hydroxide in water, with a solution of 10% by weight of sodium sulphite in water with a 1% by weight solution of sodium hydrogen-carbonate in water, and then dried by stripping in a packed column at 34° C.

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

実験手順: ##STR26## Synthesized as for 1-Acetyl-4-nonanoyl-2,5-piperazinedione in EXAMPLE I using 3,5,5-trimethylhexanoyl chloride in place of nonanoyl chloride.

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

実験手順: Following the procedure of Example 1, 6,7,8,9,10,11-Hexahydro-benzo[b]-cycloocta[d]furan-2-ylamine (0.15 g, 0.70 mmol), 3,5,5-trimethylhexanoyl chloride (0.14 mL, 0.73 mmol), and poly(vinylpyridine) (0.5 g) in dichloroethane (15 mL) provided N-(6,7,8,9,10,11-hexahydrobenzo[b]cycloocta[d]furan-2-yl)-3,5,5-trimethylhexanamide (0.25 g). MS (ESI) m/z 356 ([M+H]+).

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

実験手順: A solution of (2S)-(2-amino-5-bromo-benzoylamino)-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester (54.5 mg, 0.10 mmol) from example 294 in 1 mL dry CH2Cl2 was treated with 3,5,5-trimethylhexanoyl chloride(1.2 eq., 23 microL, 0.12 mmol) and pyridine (1.5 eq., 12 microL, 0.15 mmol) in succession and stirred under an atmosphere of dry N2 for one hour, then concentrated in vacuo. The crude residue was purified by flash column chromatography (hexanes, EtOAc) to afford the desired amide, (2S)-[5-Bromo-2-(3,3,5-trimethyl-hexanoylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester, in quantitative yield (68 mg, 100%). The methyl ester (20 mg, 29 micromol) was dissolved in 2.0 mL THF and 0.5 mL MeOH and saponified with 2N aqueous LiOH solution (0.25 mL), as described in general procedure C, to afford the title compound, (2S)-[5-Bromo-2-(3,3,5-trimethyl-hexanoylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid (20 mg, 100%), as a white solid. LCMS 673 (M+1)+. 1H NMR (400 MHz, CDCl3) 10.74 [s, 1H], 8.51 [d, 1H], 7.51 [m, 3H], 7.43 [m, 2H], 7.27–7.30 [m, 2H], 7.16–7.26 [m, 5H], 6.98 [d, 2H], 6.88 [d, 2H], 6.59 [d, 1H], 5.03 [dd, 1H], 3.28 [dq, 2H], 2.36 [m, 1H], 2.14 [m, 1H], 1.11–1.25 [m, 3H], 1.00 [s, 3H], 0.92 [s, 3H], 0.91 [d, 6H]. concentrated in vacuo The crude residue was purified by flash column chromatography (hexanes, EtOAc)

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

実験手順: To a mixture of 143.3 grams of aluminum chloride and 400 mL of benzene was added 100 grams of 3,5,5-trimethylhexanoyl chloride over a 50 minute period at a rate such that the temperature did not exceed 35° C. When the addition was complete, the mixture was stirred at room temperature for three hours. The mixture was poured over 500 grams of ice and extracted with 400 mL of ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, filtered and the solvent was removed in vacuo to give 3,5,5-trimethylhexanoylbenzene. did not exceed 35° C When the addition extracted with 400 mL of ethyl acetate The organic phase was washed with brine dried over magnesium sulfate filtered the solvent was removed in vacuo