Methyl 2,5-Dibromopentanoate

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

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

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

Procedure: In a manner similar to that of Reference Example 5, 5,6,7,8-tetrahydro-1-nitro-2-naphthol was allowed to react with methyl 2,5-dibromovalerate to give methyl 5-bromo-2(5,6,7,8-tetrahydro-1-nitro-2-naphthyloxy)valerate, which was then allowed to react, in a manner similar to that of Reference Example 8, with 1-(4-fluorophenyl)piperazine to obtain methyl 5-[4-(4-fluorophenyl)-1-piperazinyl]-2-(5,6,7,8-tetrahydro-1-nitro-2-naphthyloxy)valerate as an oily product. The overall yield was 65.1%. NMR(CDCl3)δ: 1.55-2.17(8H,m), 2,41(2H,5,J=7.2 Hz), 2.52-2.81(8H,m), 2.96-3.14(4H,m), 3.72(3H,s), 4.67(1H,t,J=6 Hz), 6.55-7.11 (6H,m)

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

Procedure: In a manner similar to that of Reference Example 5, 4,5-methylenedioxy-2-nitrophenol was allowed to react with methyl 2,5-dibromovalerate to give methyl 5-bromo-2-(4,5-methylenedioxy-2-nitrophenoxy)valerate, which was then allowed to react, in a manner similar to that of Reference Example 8, with 1-(4-fluorophenyl)piperazine to obtain methyl 5-[4-(4-fluorophenyl)-1-piperazinyl]-2-(4,5-methylenedioxy-2-nitrophenoxy)valerate as crystals, m.p. 98°-99° C. The overall yield was 15.6%.

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

Procedure: By a process similar to that of Reference Example 5, ethyl 3-hydroxy-4-nitrobenzoate was allowed to react with methyl 2,5-dibromovalerate to give methyl 5-bromo-2-(5-ethoxycarbonyl-2-nitrophenoxy)valerate as an oily product (yield: 80.2%). This product was subjected to catalytic reduction to obtain ethyl 2-(3-bromopropyl)-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-7-carboxylate, m.p. 118°-119° C. The yield was 90.7%.

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

Procedure: A mixture of 2-nitrophenol (0.7 g), powdery potassium carbonate (0.7 g), methyl 2,5-dibromovalerate (1.37 g) and dimethylformamide (10 ml) was stirred at room temperature for 4 hours, to which was added ice-water, followed by extraction with ether. The ether layer was washed with water and dried (MgSO4), then the solvent was distilled off. The residue was purified by means of silica gel chromatography [eluted with hexane-ethyl acetate (1:4)] to obtain methyl 5-bromo-2-(2-nitrophenoxy)valerate as an oily product. The yield was 1.30 g (77.8%). followed by extraction with ether The ether layer was washed with water dried (MgSO4) the solvent was distilled off The residue was purified by means of silica gel chromatography [eluted with hexane-ethyl acetate (1:4)]

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

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

Procedure: To a solution of 3.06 g of 2-amino-4,5-dimethylthiophenol in 50 ml of dimethylformamide was added 5.48 g of methyl 2,5-dibromovalerate at room temperature with stirring. The mixture was stirred for 14 hours, poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated. The residue was washed with a mixture of ether and hexane to obtain 4.35 g (69.3%) of 2-(3-bromopropyl)-6,7-dimethyl-2H-1,4-benzothiazin-3(4H)-one as crystals. Recrystallization from methanol gave prisms, m.p. 151°-153° C. The mixture was stirred for 14 hours extracted with ethyl acetate The ethyl acetate layer was washed with water dried (MgSO4) concentrated The residue was washed with a mixture of ether and hexane

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

Procedure: In analogy to the procedure described in example 15B, 1-(3-trifluoromethoxy-phenyl)-[1,4]diazepan-5-one and (rac)-2,5-dibromo-pentanoic acid methyl ester gave the title compound in 92% yield as colorless oil. MS: 469.1 (1Br, MH+).

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

Procedure: In analogy to the procedure described in example 15B, 1-(3-trifluoromethyl-phenyl)-[1,4]diazepan-5-one (example 15 A) and (rac)-2,5-dibromo-pentanoic acid methyl ester gave the title compound in 97% yield as yellow oil. MS: 453.1 (1Br, MH+).

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

Procedure: In analogy to the procedure described in example 15B, 1-(3-trifluoromethyl-phenyl)-[1,4]diazepan-5-one (example 15 A) and (rac)-2,5-dibromo-pentanoic acid methyl ester gave the title compound in 97% yield as yellow oil. MS: 453.1 (1Br, MH+).

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

Procedure: Methyl (RS)-2,5-dibromovalerate (24.5 g) and toluene (19.8 g) were added to a 49% aqueous potassium carbonate solution (53.3 g), and heated to 80° C. (S)-α-methylbenzylamine (12.0 g) was added dropwise to the mixture obtained above at that temperature, and was stirred at that temperature for 9.5 hours. Water (33.9 g) was added to the reaction mixture, and then the organic layer was separated from the resulting mixture. Separated organic layer was washed with water, a 1% aqueous hydrochloric acid solution and water in this order, and concentrated under reduced pressure. Thus, N-[(S)-α-methylbenzyl]-(RS)-proline methyl ester (16.3 g) was obtained in a yield of 77.8%. was added dropwise to the mixture obtained above at that temperature the organic layer was separated from the resulting mixture Separated organic layer was washed with water a 1% aqueous hydrochloric acid solution and water in this order, and concentrated under reduced pressure