GFHUSRSVULITGF-UHFFFAOYSA-N synthesis

Yield:905589-94-8 74.7%

Reaction Conditions:

Stage #1: i-pentyl bromidewith magnesium in tetrahydrofuran at 20; for 3 h;
Stage #2: ethyl 5-bromovaleratewith 1-methyl-pyrrolidin-2-one;copper(l) chloride in tetrahydrofuran at 0; for 2.41667 h;Product distribution / selectivity;

Steps:

1

[Example 1] Synthesis of 8-methylnonanoic acid (example of cross coupling method); Under an argon atmosphere, Mg turnings (6.12 g, 252 mmol) was suspended in THF (10 ml) . 200 mg from isopentyl bromide (34.6 g, 229 mmol) was added at room temperature, and exothermic heat and foaming were confirmed. THF (50 ml) was added, and a solution of whole remainder of isopentyl bromide in THF (65 ml) was slowly added dropwise at room temperature over 1 hr and the mixture was stirred for 2 hrs. At this time, mild refluxing state was achieved. The reaction solution was filtered through cotton plug while washing with THF to give a solution (total amount 180 ml) of isopentylmagnesium bromide in THF.Under an argon atmosphere, copper (I) chloride (426 mg, 4.30 mmol) was dissolved in NMP (55.2 ml, 575 mmol). The EPO reaction vessel was cooled to 0⁰C (ice bath) , and a solution of ethyl 5-bromovalerate (30.0 g, 144 mmol) in THF (35 ml) was added dropwise over 10 min. The THF solution of isopentylmagnesium bromide prepared in advance was slowly added dropwise at 0⁰C (ice bath) over 1.5 hrs. After further stirring at the same temperature for 45 min, the reaction was carefully quenched with saturated aqueous ammonium chloride solution (200 ml) , and the mixture was extracted twice with heptane (200 ml) . The combined heptane layer was washed with saturated aqueous ammonium chloride solution (100 ml) , water (100 ml) and saturated brine (100 ml) , dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a pale-yellow oil (30.8 g) . 29.6 g therefrom was distilled under reduced pressure (1.2 mmHg, 69-71°C) to give ethyl 8-methylnonanoate (20.6 g, yield 74.7%) as a colorless transparent oil.¹H-NMR (CDCl₃, δ) : 0.860 (d, 6H, J=6.63Hz), 1.13-1.33 (m, HH), 1.48-1.64 (m, 3H), 2.28 (t, 2H, J=7.55Hz), 4.12(q, 2H, J=7.13Hz) . ¹³C-NMR (CDCl₃, δ) : 14.60, 22.98, 25.36, 27.56, 28.30, 29.54, 29.89, 34.75, 39.31, 60.47, 174.2.

References:

WO2006/88239,2006,A1 Location in patent:Page/Page column 34-35