butanoyl butanoate

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

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

Procedure: Using the method described above for the preparation of 4-acetamido-2,6-dichlorophenol (but using butyric anhydride in place of acetic anhydride) there was obtained 4-butyramido-2,-6-dichlorophenol (used as starting material in Example 51) as a solid, m.p. 146°-147°; NMR([CD3 ]2SO): 0.9(3H,t), 1.58(2H,m), 2.25(2H,t), 7.62(2H,s), 9.75(1H,br s) and 9.85(1H,s); m/z 248(M+H).

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

Procedure: To a solution of 4-{3E-[5-(1H-indol-2-yl)-2,4-dimethoxyphenyl]acryloyl}benzenesulfonamide (Ex-35E, 0.92 g, 2 mmol), DMAP(0.024 g, 0.2 mmol) and Et3N (0.2 g, 2.1 mmol) in 100 ml o THF was added butyric anhydride (0.64 g, 4 mmol). The reaction mixture was stirred at room temperature overnight. The clear solution was then poured into 150 ml of H2O and extracted with CH2Cl2. The combined organic phase was washed with water, dried over MgSO4, and concentrated to dryness. Recrystallization from EtOAc/hexenes gave 0.80 g (75%) of the title compound as a red solid, mp 155–165° C. 1H-NMR (300 MHz, Acetone-d6) δ 10.55 (br, 1H), 8.35 (s, 1H), 8.27 (d, J=8 Hz, 2H), 8.13–8.20 (m, 3H), 7.89 (d, J=16 Hz, 1H), 7.52 (d, J=7 Hz, 1H), 7.39 (d, J=8 Hz, 1H), 7.02–7.07(m, 1H), 6.95–7.00 (m, 2H), 6.90 (s, 1H), 4.10 (s, 3H), 4.04 (s, 3H), 2.29 (t, J=8 Hz, 2H), 1.48–1.56 (m, 2H), 0.81(t, J=8 Hz, 3H). extracted with CH2Cl2 The combined organic phase was washed with water dried over MgSO4 concentrated to dryness Recrystallization from EtOAc/hexenes

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

Procedure: The following run illustrates the metathetical reaction of impure heptafluorobutyryl fluoride with butyric acid in the presence of butyric anhydride to give heptafluorobutyric acid and butyryl fluoride and the recovery of products from the reaction mixture by fractional distillation.

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

Procedure: The following run illustrates the metathetical reaction of impure heptafluorobutyryl fluoride with butyric acid in the presence of butyric anhydride to give heptafluorobutyric acid and butyryl fluoride and the recovery of products from the reaction mixture by fractional distillation.

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

Procedure: A solution of dibenzyl N-(N-tert-butoxycarbonyl-L-valyl)-L-glutamate (1 g) and anisole (0.5 ml) in trifluoroacetic acid (2 ml) was stirred at 0° C. for 1 hour. Evaporation of trifluoroacetic acid under reduced pressure gave a residue which was taken up in benzene. Benzene was distilled off by using high vacuum pump. This operation was repeated three times to leave crude dibenzyl N-L-valyl-L-glutamate, which was dissolved in chloroform (20 ml). To this solution were added triethylamine (3 ml) and butyric anhydride (0.5 ml) and the resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into ice water and the separated organic layer was washed with dilute hydrochloric acid solution, a saturated aqueous solution of sodium bicarbonate and brine respectively. After solvent was evaporated, the residue was recrystallized from petroleum ether to afford dibenzyl N-(N-butanoyl-L-valyl)-L-glutamate (613 mg) as crystals. Evaporation of trifluoroacetic acid under reduced pressure gave a residue which Benzene was distilled off to leave crude dibenzyl N-L-valyl-L-glutamate, which the separated organic layer was washed with dilute hydrochloric acid solution After solvent was evaporated the residue was recrystallized from petroleum ether

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

Procedure: A solution of 31.64 g(0.2 mol) ethyl butyryl acetate and 5 mol of ethanol is added dropwise over a period of 5 min. to a solution of 38.7 g(0.6 mol) ethylamine (70% in water) and 50 ml of water (exotherm from 28° C. to 33° C. observed). The mixture is stirred at room temperature for 18 hrs. and is extracted with three 100 ml portions of methylene dichloride (MDC). The methylene dichloride extract is dried over magnesium sulfate and concentrated in vacuo to afford 30.7 g(83% yield) of product, a colorless oil. and is extracted with three 100 ml portions of methylene dichloride (MDC) The methylene dichloride extract is dried over magnesium sulfate concentrated in vacuo

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

Procedure: A solution of 31.64 g(0.2 mol) ethyl butyryl acetate and 5 mol of ethanol is added dropwise over a period of 5 min. to a solution of 38.7 g(0.6 mol) ethylamine (70% in water) and 50 ml of water (exotherm from 28° C. to 33° C. observed). The mixture is stirred at room temperature for 18 hrs. and is extracted with three 100 ml portions of methylene dichloride (MDC). The methylene dichloride extract is dried over magnesium sulfate and concentrated in vacuo to afford 30.7 g(83% yield) of product, a colorless oil. and is extracted with three 100 ml portions of methylene dichloride (MDC) The methylene dichloride extract is dried over magnesium sulfate concentrated in vacuo

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

Procedure: Rearrangement of CAMC was accomplished in high yield by refluxing the allyl ether from Step 2 (143.5 gm; 0.55 mole) in a mixture of p-diisopropylbenzene (Aldrich, 1000 ml) and butyric anhydride (96 ml, 92.8 gm; 0.59 mol, Aldrich) under argon for 18 hours. The cooled reaction mixture was diluted with chloroform, washed with water and then saturated sodium bicarbonate, dried (MgSO4) then evaporated under reduced pressure. Following recrystallization from ethanol, 79.9 grams of mixed 6 and 8-(β-chloroallyl)-7-butyroxy-4-methylcoumarin (BCAMC,15) were obtained. HPLC analysis (Beckman; C18-ODS reverse phase column, isocratic elution with 60% CH3OH/40% H2O ) showed the mixture to contain 85.7% of the desired 8-substituted isomer, of which a sample was purified by column chromatography (60-200 mesh silica gel, elution with CH2Cl2). The structures of the two isomers were confirmed by NMR. NMR (CDCl3) d 7.56 (1H, d), 7.11 (1H, d), 6.26 (1h, d), 5.05-5.19 (2H, m) , 3.84 (2H, m), 2.55-2.62 (2H, m), 2.43 (3H, d) , 1.78-1.82 (2H, m), 1.01-1.09 (3H, t). in high yield The cooled reaction mixture washed with water saturated sodium bicarbonate, dried (MgSO4) then evaporated under reduced pressure recrystallization from ethanol, 79.9 grams of mixed 6

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

Procedure: Rearrangement of CAMC was accomplished in high yield by refluxing the allyl ether from Step 2 (143.5 gm; 0.55 mole) in a mixture of p-diisopropylbenzene (Aldrich, 1000 ml) and butyric anhydride (96 ml, 92.8 gm; 0.59 mol, Aldrich) under argon for 18 hours. The cooled reaction mixture was diluted with chloroform, washed with water and then saturated sodium bicarbonate, dried (MgSO4) then evaporated under reduced pressure. Following recrystallization from ethanol, 79.9 grams of mixed 6 and 8-(β-chloroallyl)-7-butyroxy-4-methylcoumarin (BCAMC,15) were obtained. HPLC analysis (Beckman; C18-ODS reverse phase column, isocratic elution with 60% CH3OH/40% H2O ) showed the mixture to contain 85.7% of the desired 8-substituted isomer, of which a sample was purified by column chromatography (60-200 mesh silica gel, elution with CH2Cl2). The structures of the two isomers were confirmed by NMR. NMR (CDCl3) d 7.56 (1H, d), 7.11 (1H, d), 6.26 (1h, d), 5.05-5.19 (2H, m) , 3.84 (2H, m), 2.55-2.62 (2H, m), 2.43 (3H, d) , 1.78-1.82 (2H, m), 1.01-1.09 (3H, t). in high yield The cooled reaction mixture washed with water saturated sodium bicarbonate, dried (MgSO4) then evaporated under reduced pressure recrystallization from ethanol, 79.9 grams of mixed 6

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

Procedure: A solution of 31.64 g (0.2 mol) ethyl butyryl acetate and 5 ml of ethanol is added dropwise over a period of 5 min. to a solution of 38.7 g (0.6 mol) ethylamine (70% in water) and 50 ml of water (exotherm from 28° C. to 33° C. observed). The mixture is stirred at room temperature for 18 hrs. and is extracted with three 100 ml portions of methylene dichloride (MDC). The methylene dichloride extract is dried over magnesium sulfate and concentrated in vacuo to afford 30.7 g (83% yield) of product, a colorless oil. and is extracted with three 100 ml portions of methylene dichloride (MDC) The methylene dichloride extract is dried over magnesium sulfate concentrated in vacuo

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

Procedure: Molar quantities of butyric acid and butyryl chloride are heated together on a water-bath for 1 hour and then boiled for 7 hours in an oil-bath. Butyric anhydride, b.p. 198°-199° C./765 mm, is obtained on distillation of the resulting mixture.