ETHYL 3-BROMOBUTYRATE

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

Procedure: A reaction vessel was charged with 2.02 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 1.56 g of ethyl 3-bromobutyrate, 1.11 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.54 g of ethyl 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxybutyrate (90% yield). extracted twice with 50 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: A reaction vessel was charged with 2.02 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 1.56 g of ethyl 3-bromobutyrate, 1.11 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.54 g of ethyl 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxybutyrate (90% yield). extracted twice with 50 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: To a solution of ethyl 3-bromobutanoate (6.0 mL, 42 mmol) in N,N-dimethylformamide (20 mL) at 0° C. was added piperidine (8.0 mL, 80 mmol) and the mixture was warmed to room temperature then stirred 16 h. The reaction mixture was diluted with ethyl acetate (200 mL) and washed with a solution of brine and 2.0M aqueous sodium hydroxide (4:1 v/v). The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated to give ethyl 4-piperidin-1-ylbutanoate (6.8 g, 81% yield) as brown oil. MS (EI) for C11H21NO2: 200 (MH+). washed with a solution of brine and 2.0M aqueous sodium hydroxide (4:1 v/v) The organic phase was then dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: To a solution of ethyl 3-bromobutanoate (6.0 mL, 42 mmol) in N,N-dimethylformamide (20 mL) at 0° C. was added piperidine (8.0 mL, 80 mmol) and the mixture was warmed to room temperature then stirred 16 h. The reaction mixture was diluted with ethyl acetate (200 mL) and washed with a solution of brine and 2.0M aqueous sodium hydroxide (4:1 v/v). The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated to give ethyl 4-piperidin-1-ylbutanoate (6.8 g, 81% yield) as brown oil. MS (EI) for C11H21NO2: 200 (MH+). washed with a solution of brine and 2.0M aqueous sodium hydroxide (4:1 v/v) The organic phase was then dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: The title compound was synthesized according to the procedure described for the preparation of Example 458 using 70 (160 mg, 0.76 mmol) and ethyl 3-bromobutanoate (0.01 mL, 0.91 mmol) to provide 460 (32 mg, 13% yield) as a white powder. LC-MS (M+H=326, obsd.=326). 1H NMR (400 MHz, DMSO-D6) δ 8.53 (ddd, J=1.7, 6.4, 9.7, 2H), 8.03 (d, J=8.6, 1H), 7.27 (m, 2H), 6.88 (dd, J=2.1, 8.7, 1H), 6.14 (s, 2H), 4.47 (t, J=6.9, 2H), 3.97 (q, J=7.1, 2H), 2.33 (t, J=7.4, 2H), 1.95 (p, J=7.3, 2H), 1.12 (t, J=7.1, 3H). The title compound was synthesized

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

Procedure: A solution of 4-benzyloxyphenol (4.2 g) in dimethyl formamide (50 ml) was treated with sodium hydride (840 mg of a 60% dispersion), and the mixture stirred until evolution of gas ceased. There was then added ethyl 3-bromobutyrate (2.9 ml), and the solution stirred overnight. It was then poured into water (300 ml) and the mixture extracted with ether (3×50 ml). The combined extracts were washed with water (3×) and brine, dried (MgSO4) and evaporated to give a crude product as a brown oil (6 g). This was purified by chromatography on silica, eluting with hexane containing increasing amounts of ethyl acetate to give ethyl 3-(4-benzyloxyphenoxy)butyrate as a colourless crystalline solid (4.5 g) NMR (d6DMSO): δ1.25 (3H,t);1.8-2.0 (2H,m); 2.45 (2H,t); 3.9 (2H,t); 4.1 (2H,q); 5.0 (2H,s); 6.8-7.0 (4H,m); 7.4 (5H,m); m/e 314 (M+H)+. the mixture extracted with ether (3×50 ml) The combined extracts were washed with water (3×) and brine dried (MgSO4) evaporated to give a crude product as a brown oil (6 g) This was purified by chromatography on silica eluting with hexane containing increasing amounts of ethyl acetate

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

Procedure: A reaction vessel was charged with 2.02 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 1.56 g of ethyl 3-bromobutyrate, 1.11 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.54 g of ethyl 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxybutyrate (90% yield). extracted twice with 50 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: A reaction vessel was charged with 2.02 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 1.56 g of ethyl 3-bromobutyrate, 1.11 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.54 g of ethyl 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxybutyrate (90% yield). extracted twice with 50 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: In the same manner as in Reference Example 3, except that an equimolar amount of 3-hexyloxy-4,8-dihydroxy-2H-1-benzopyran-2-one was used in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, and ethyl 3-bromobutanoate was used in place of ethyl bromoacetate in Reference Example 3, 3-hexyloxy-4-hydroxy-8-(3-ethoxycarbonylpropyloxy)-2H-1-benzopyran-2-one was obtained.

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

Procedure: In the same manner as in Reference Example 3, except that an equimolar amount of 3-hexyloxy-4,8-dihydroxy-2H-1-benzopyran-2-one was used in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, and ethyl 3-bromobutanoate was used in place of ethyl bromoacetate in Reference Example 3, 3-hexyloxy-4-hydroxy-8-(3-ethoxycarbonylpropyloxy)-2H-1-benzopyran-2-one was obtained.

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

Procedure: A reaction vessel was charged with 2.02 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 1.56 g of ethyl 3-bromobutyrate, 1.11 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.54 g of ethyl 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxybutyrate (90% yield). extracted twice with 50 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: A reaction vessel was charged with 2.02 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 1.56 g of ethyl 3-bromobutyrate, 1.11 g of potassium carbonate and 20 ml of N,N-dimethylformamide. After stirring at room temperature for 12 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 2.54 g of ethyl 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxybutyrate (90% yield). extracted twice with 50 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product