Sodium Hydroxide → 6-Hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid

Participants

Reaction Steps

In a dried flask under N2, a suspension of 47.2 (1.10 mol) of 56 percent by weight sodium hydride in mineral oil in 1000 ml of tetrahydrofuran was stirred as 209.4 g (1.15 mol) of trimethyl phosphonoacetate was added over 2.25 hr. The white paste was stirred for 0.25 hr and then a solution of 132.2 g (0.50 mol) of (±)-6-acetoxy-2-hydroxy-2,5,7,8-tetramethylchroman in 1000 ml of tetrahydrofuran was added over 0.50 hr. The pale yellow suspension was stirred at 23°C for 18 hours and then heated at reflux for 4.0 hours. The cooled solutions from two such reactions were stripped of solvent and worked up and dried by the procedure given in Example 1 to give a cloudy red-brown oil containing (±)-methyl (6-acetoxy-2,5,7,8-tetramethylchroman-2-yl)acetate. To a solution of this material in 2000 ml. of ethanol, there was added 2000 ml. of H2O and 240 g. (6.0 mol.) of NaOH. The solution was stirred at 23°C. for 4 hours, washed with petroleum ether (b.p. 30°-60°C.), diluted with 6000 ml. of ice-H2O and acidified by the dropwise addition over 0.50 hour of 600 ml. of concentrated aqueous HCl. The solid was removed by filtration, washed with H2O and crystallized from ethanol-H2O to give (±) -(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetic acid as a light tan powder: m.p. 168°-171°C.

Provenance & Evidence