BenzeneMethanol, 5-(1,1-diMethylethyl)-2-(phenylMethoxy)- synthesis

Yield:-

Reaction Conditions:

Stage #1: 2-(benzyloxy)-5-tert-butylbenzaldehydewith sodium tetrahydroborate in methanol at 0 - 20;
Stage #2: with hydrogenchloride;water in methanol at 20;

Steps:

1; 3; 4

To a stirred suspension of compound 3 (974 g, 3.63 mol) in MeOH (4000 mL) was slowly added NaBH₄ (121 g, 3.20 mol) at 0-20 ⁰C. The solution was left stirring at 15 ⁰C for 3 hours, and then cooled to 0 °C. 2N HCl (aq) (1300 mL) was added dropwise at below 20 ⁰C. The solution was then filtered and evaporated to dryness, and the residue was dissolved in MTBE (5 L). The solution was then washed with water (2 Lx2) and brine (1.5 LxI). Evaporation of the solvent gave compound 4 as a light-yellow solid which was used in the next reaction without further purification. ¹H NMR (DMSO-d₆; 400 MHz) δ 7.40 (m), δ 7.32 (m), δ 7.17 (m), δ 6.91 (m), δ 5.09 (s), δ 5.00 (t), δ 4.56 (d), 5 1.26 (s).

References:

WO2010/108155,2010,A1 Location in patent:Page/Page column 14-15; 35-36; 45