methyl 3-methylbutanoate

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.4 mL (18.49 mmol, 1.5 eq) of isopropylamine in 50 mL of dry THF at -78° C. under argon is added 9.3 mL (14.8 mmol, 1.2 eq) of 1.6 M BuLi in hexanes solution. This is stirred at -78° C. for 1 hour at which time 1.8 mL (13.56 mmol, 1.1 eq) of methyl isovalerate is added dropwise. This mixture is stirred at -78° C. for 1.5 hours at which time 2 g (12.33 mmol) of 5-phenylpentanal in 10 mL of dry THF is added dropwise. This is stirred at -78° C. for 1 hour, then allowed to warm slowly to 0° C. over 3 hours. The reaction is quenched with saturated NH4Cl solution and then partitioned between ether and saturated NH4Cl solution. The organics are dried (Na2SO4) and concentrated in vacuo. The product is purified by flash silica gel chromatography to afford methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate in the form of a yellow oil. (0.88 g, 26%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 0.95(t, 6H), 1.45(m, 3H), 1.6(m, 3H), 2.08(bs, 1H), 2.15(m, 1H), 2.35(t, 1H), 2.6(t, 2H), 3.68(s, 3H), 3.85(bm, 1H), 7.15(m, 3H), 7.25(m, 2H). is added dropwise is added dropwise to warm slowly to 0° C. over 3 hours The reaction is quenched with saturated NH4Cl solution partitioned between ether and saturated NH4Cl solution The organics are dried (Na2SO4) concentrated in vacuo The product is purified by flash silica gel chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.4 mL (18.49 mmol, 1.5 eq) of isopropylamine in 50 mL of dry THF at -78° C. under argon is added 9.3 mL (14.8 mmol, 1.2 eq) of 1.6 M BuLi in hexanes solution. This is stirred at -78° C. for 1 hour at which time 1.8 mL (13.56 mmol, 1.1 eq) of methyl isovalerate is added dropwise. This mixture is stirred at -78° C. for 1.5 hours at which time 2 g (12.33 mmol) of 5-phenylpentanal in 10 mL of dry THF is added dropwise. This is stirred at -78° C. for 1 hour, then allowed to warm slowly to 0° C. over 3 hours. The reaction is quenched with saturated NH4Cl solution and then partitioned between ether and saturated NH4Cl solution. The organics are dried (Na2SO4) and concentrated in vacuo. The product is purified by flash silica gel chromatography to afford methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate in the form of a yellow oil. (0.88 g, 26%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 0.95(t, 6H), 1.45(m, 3H), 1.6(m, 3H), 2.08(bs, 1H), 2.15(m, 1H), 2.35(t, 1H), 2.6(t, 2H), 3.68(s, 3H), 3.85(bm, 1H), 7.15(m, 3H), 7.25(m, 2H). is added dropwise is added dropwise to warm slowly to 0° C. over 3 hours The reaction is quenched with saturated NH4Cl solution partitioned between ether and saturated NH4Cl solution The organics are dried (Na2SO4) concentrated in vacuo The product is purified by flash silica gel chromatography

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

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

Procedure: A mixture of 1.0 g of 2,2-dimethylcyclopropanecarboxamide, 2.4 g. of 2-ketoadipic acid and 25 ml. of methyl isovalerate was heated under reflux for 4 hrs, with removal of H2O by a modified Dean-Stark trap containing molecular sieves (4A). After standing at room temperature overnight, the crystalline precipitate was filtered, washed with ether and recrystallized from ethyl acetate to give 0.23 g. of product, m.p. 163°-165°. The NMR spectrum was consistent with the desired structure. the crystalline precipitate was filtered washed with ether recrystallized from ethyl acetate to give 0.23 g

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

Procedure: A mixture of 1.0 g. of 2,2-dimethylcyclopropanecarboxamide, 2.4 g. of 2-ketoadipic acid and 25 ml. of methyl isovalerate was heated under reflux for 4 hrs, with removal of H2O by a modified Dean-Stark trap containing molecular sieves (4A). After standing at room temperature overnight, the crystalline precipitate was filtered, washed with ether and recrystallized from ethyl acetate to give 0.23 g. of product, m.p. 163°-165°. The NMR spectrum was consistent with the desired structure. A mixture of 1.0 g the crystalline precipitate was filtered washed with ether recrystallized from ethyl acetate to give 0.23 g

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

Procedure: A mixture of 1.0 g. of 2,2-dimethylcyclopropanecarboxamide, 2.4 g. of 2-ketoadipic acid and 25 ml. of methyl isovalerate was heated under reflux for 4 hrs, with removal of H2O by a modified Dean-Stark trap containing molecular sieves (4A). After standing at room temperature overnight, the crystalline precipitate was filtered, washed with ether and recrystallized from ethyl acetate to give 0.23 g. of product, m.p. 163°-165°. The NMR spectrum was consistent with the desired structure. A mixture of 1.0 g the crystalline precipitate was filtered washed with ether recrystallized from ethyl acetate to give 0.23 g

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

Procedure: A mixture of 1.0 g. of 2,2-dimethylcyclopropanecarboxamide, 2.4 g. of 2-ketoadipic acid and 25 ml. of methyl isovalerate was heated under reflux for 4 hrs, with removal of H2O by a modified Dean-Stark trap containing molecular sieves (4A). After standing at room temperature overnight, the crystalline precipitate was filtered, washed with ether and recrystallized from ethyl acetate to give 0.23 g. of product, m.p. 163°-165°. The NMR spectrum was consistent with the desired structure. A mixture of 1.0 g the crystalline precipitate was filtered washed with ether recrystallized from ethyl acetate to give 0.23 g

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

Procedure: A mixture of 1.0 g. of 2,2-dimethylcyclopropanecarboxamide, 2.4 g. of 2-ketoadipic acid and 25 ml. of methyl isovalerate was heated under reflux for 4 hrs, with removal of H2O by a modified Dean-Stark trap containing molecular sieves (4A). After standing at room temperature overnight, the crystalline precipitate was filtered, washed with ether and recrystallized from ethyl acetate to give 0.23 g. of product, m.p. 163°-165°. The NMR spectrum was consistent with the desired structure. A mixture of 1.0 g the crystalline precipitate was filtered washed with ether recrystallized from ethyl acetate to give 0.23 g

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.4 mL (18.49 mmol, 1.5 eq) of isopropylamine in 50 mL of dry THF at -78° C. under argon is added 9.3 mL (14.8 mmol, 1.2 eq) of 1.6 M BuLi in hexanes solution. This is stirred at -78° C. for 1 hour at which time 1.8 mL (13.56 mmol, 1.1 eq) of methyl isovalerate is added dropwise. This mixture is stirred at -78° C. for 1.5 hours at which time 2 g (12.33 mmol) of 5-phenylpentanal in 10 mL of dry THF is added dropwise. This is stirred at -78° C. for 1 hour, then allowed to warm slowly to 0° C. over 3 hours. The reaction is quenched with saturated NH4Cl solution and then partitioned between ether and saturated NH4Cl solution. The organics are dried (Na2SO4) and concentrated in vacuo. The product is purified by flash silica gel chromatography to afford methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate in the form of a yellow oil. (0.88 g, 26%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 0.95(t, 6H), 1.45(m, 3H), 1.6(m, 3H), 2.08(bs, 1H), 2.15(m, 1H), 2.35(t, 1H), 2.6(t, 2H), 3.68(s, 3H), 3.85(bm, 1H), 7.15(m, 3H), 7.25(m, 2H). is added dropwise is added dropwise to warm slowly to 0° C. over 3 hours The reaction is quenched with saturated NH4Cl solution partitioned between ether and saturated NH4Cl solution The organics are dried (Na2SO4) concentrated in vacuo The product is purified by flash silica gel chromatography