Lithium Hydroxide → 1-((3aS,8aR)-8,8a-Dihydro-2,2-dimethyl-2H-indeno(1,2-d)oxazol-3(3aH)-yl)-3-phenyl-1-propanone

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Reaction Steps

Solid lithium hydroxide (anhydrous) (21.55 g, 0.9 mole, 0.9 equiv.) was added to a 3-neck Morton flask equipped with a mechanical stirrer, condenser, thermocouple and nitrogen. Solid (−)-cis-aminoindan-2-ol (3, 149.19 g, 1.0 mole) was then added, followed by dry THF (1.492 L, to give ˜100 g/l batch) at 20° C. The resulting slurry was stirred at 350 RPM. The KF of the solution was <1200 mg/l. 2-Methoxypropene (383.1 ml, 288.47 g, 4.0 mole, 4.0 equiv.) was then added subsurfacely. The flask was then placed in a 20° C. water bath, and neat hydrocinnamoyl chloride (2, 153.02 ml, 173.68 g, 1.03 mole, 1.03 equiv.) was added over 1.25 hours. At about 50% hydrocinnamoyl chloride addition, the solution became clear. At about 90% addition an exotherm occured (5-10° C.). Upon completion of the addition of 2 the batch was warmed to 40° C. and aged until >99.0% conversion (as measured by HPLC assay) to acetonide 1 was achieved. Additional lithium hydroxide (5.99 g, 0.25 mole, 0.25 eq.) was added to the batch to quench excess HCl by-product. The batch was stirred for one hour. Upon quench the batch turned from clear to golden in appearance. Residual HCl was determined by titration to be less than 0.005 mmol. The solution yield was 98%.

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