ethyl 7-bromo-2,2-dimethylheptanoate

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:

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: p-[3-(1-Imidazolyl)propoxy]phenol and ethyl 7-bromo-2,2-dimethylheptanoate were used as starting compounds in place of p-[5-(1-imidazolyl)pentyloxy]phenol and ethyl 6-bromo-2,2-dimethylhexanoate, respectively, in EXAMPLE 30. The starting compounds were heated and treated in a manner similar to EXAMPLE 30 to give the desired product, ethyl 7-[p-[3-(1-imidazolyl)propoxy]phenoxy]-2,2-dimethylheptanoate, as an oily substance. The starting compounds were heated treated in a manner similar to EXAMPLE 30

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

実験手順: Ethyl-2,2-dimethyl-7-bromoheptanoate (7.0 g, 0.026 mol) was treated with 4-chlorobenzenesulphonamide (9.9 g, 0.052 mol) and potassium carbonate (21.5 g, 0.016 mol) by the method described in Example 5(ii) to give the title compound (1.3 g) as an oil.

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

実験手順: Using the method described in Example 5(i). 1,5-dibromopentane (23 g, 0.1 mol) and ethylisobutyrate (10.4 g, 0.09 mol) were reacted in the presence of lithium diisopropylamide (0.1 mol) and hexamethylphosphoramide (22 g) to give the title compound as an oil (7.4 g).

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

実験手順: According to the method for the synthesis of 206e, 205g (43.0 g, 0.16 mol) was treated with LiBH4 (5.55 g, 0.25 mol) and methanol (7.75 g, 0.24 mol) in CH2Cl2 (200 mL) to give 206g (36.2 g, 98%) as a colorless, viscous oil. 1H NMR (CDCl3): δ 3.41 (t, 2H, J=6.9), 3.30 (br. s, 2H), 1.90-1.84 (m, 3H), 1.42-1.22 (m, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 71.9, 38.6, 35.1, 34.1, 32.9, 29.2, 24.0, 23.2. HRMS (LSIMS, nba): Calcd for C9H18Br (MH+-H2O): 205.0592, found: 205.0563.

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

実験手順: Under argon atmosphere, a solution of 1,5-dibromopentane (500 g, 2.2 mol) and ethyl isobutyrate (221 g, 1.9 mol) in anhydrous THF (4 L) was chilled in a dry ice/acetone bath to −78° C. Over a 40 min period, LDA solution in THF (1.8 M, 1 L, 1.8 mol) was added dropwise. After the addition, the solution was allowed to stir overnight and gradually warm to room temperature. Careful quenching of the excess base by slow addition of saturated aqueous NH4Cl solution (3 L) furnished a two-phase mixture. The organic layer was separated and evaporated under vacuum to a minimum volume (ca. 1 L). The organic residue was recombined with the aqueous layer and the resulting mixture was extracted with ethyl acetate (3×1 L). The combined ethyl acetate layers were then washed with 1 N HCl (5 L), water (3 L) and saturated aqueous NaHCO3 solution (4 L) before drying over anhydrous MgSO4. Concentration in vacuo gave crude material (468.7 g), which was then purified by distillation affording 205g (208.7 g, 44%) as a colorless oil. Bp 106-108° C./0.01 mmHg. 1H NMR (CDCl3): δ 4.11 (q, 2H, J=7.2), 3.39 (t, 2H, J=6.8), 1.85 (m, 2H), 1.56-1.35 (m, 4H), 1.24 (t, 3H, J=7.2), 1.31-1.19 (m, 2H), 1.16 (s, 6H). 13C NMR (CDCl3): δ 177.9, 60.2, 42.1, 40.5, 33.8, 32.6, 28.6, 25.2, 24.2, 14.3. HRMS (EI): Calcd for C11H22BrO2 (MH+) 265.0803, found 265.0810. After the addition Careful quenching of the excess base by slow addition of saturated aqueous NH4Cl solution (3 L) furnished a two-phase mixture The organic layer was separated evaporated under vacuum to a minimum volume (ca. 1 L) the resulting mixture was extracted with ethyl acetate (3×1 L) The combined ethyl acetate layers were then washed with 1 N HCl (5 L), water (3 L) and saturated aqueous NaHCO3 solution (4 L) before drying over anhydrous MgSO4 Concentration in vacuo gave crude material (468.7 g), which was then purified by distillation

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

実験手順: Under argon atmosphere, a solution of 1,5-dibromopentane (500 g, 2.2 mol) and ethyl isobutyrate (221 g, 1.9 mol) in anhydrous THF (4 L) was chilled in a dry ice/acetone bath to −78° C. Over a 40 min period, LDA solution in THF (1.8 M, 1 L, 1.8 mol) was added dropwise. After the addition, the solution was allowed to stir overnight and gradually warm to room temperature. Careful quenching of the excess base by slow addition of saturated aqueous NH4Cl solution (3 L) furnished a two-phase mixture. The organic layer was separated and evaporated under vacuum to a minimum volume (ca. 1 L). The organic residue was recombined with the aqueous layer and the resulting mixture was extracted with ethyl acetate (3×1 L). The combined ethyl acetate layers were then washed with 1 N HCl (5 L), water (3 L) and saturated aqueous NaHCO3 solution (4 L) before drying over anhydrous MgSO4. Concentration in vacuo gave crude material (468.7 g), which was then purified by distillation affording 205g (208.7 g, 44%) as a colorless oil. Bp 106-108° C./0.01 mmHg. 1H NMR (CDCl3): δ 4.11 (q, 2H, J=7.2), 3.39 (t, 2H, J=6.8), 1.85 (m, 2H), 1.56-1.35 (m, 4H), 1.24 (t, 3H, J=7.2), 1.31-1.19 (m, 2H), 1.16 (s, 6H). 13C NMR (CDCl3): δ 177.9, 60.2, 42.1, 40.5, 33.8, 32.6, 28.6, 25.2, 24.2, 14.3. HRMS (EI): Calcd for C11H22BrO2 (MH+) 265.0803, found 265.0810. After the addition Careful quenching of the excess base by slow addition of saturated aqueous NH4Cl solution (3 L) furnished a two-phase mixture The organic layer was separated evaporated under vacuum to a minimum volume (ca. 1 L) the resulting mixture was extracted with ethyl acetate (3×1 L) The combined ethyl acetate layers were then washed with 1 N HCl (5 L), water (3 L) and saturated aqueous NaHCO3 solution (4 L) before drying over anhydrous MgSO4 Concentration in vacuo gave crude material (468.7 g), which was then purified by distillation

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

実験手順: According to the method for the synthesis of 206e, 205g (43.0 g, 0.16 mol) was treated with LiBH4 (5.55 g±0.25 mol) and methanol (7.75 g, 0.24 mol) in CH2Cl2 (200 mL) to give 206g (36.2 g, 98%) as a colorless, viscous oil. 1H NMR (CDCl3): δ 3.41 (t, 2H, J=6.9), 3.30 (br. s, 2H), 1.90-1.84 (m, 3H), 1.42-1.22 (m, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 71.9, 38.6, 35.1, 34.1, 32.9, 29.2, 24.0, 23.2. HRMS (LSIMS, nba): Calcd for C9H28Br (MH+−H2O): 205.0592, found: 205.0563.