(1S,2R)-(-)-1-Amino-2-indanol → (3S)-3-(4-Hydroxyphenyl)-4-hexynoic acid

Beteiligte Stoffe

Reaktionsschritte

A 5 L round bottom flask was charged with compound 1.3 (66.4 g, 325 mmol) and i-PrOH (1 L) and heated to 70° C. (1S, 2R)-1-amino-2-indanol (46.1 g, 309 mmol) was dissolved in i-PrOH (1 L) with gentle warming. The solution of amine was added to the dissolved carboxylic acid and the resulting solution was allowed to cool to room temperature. After 16 hours, the crystals were collected and dried. The salt was re-suspended in 2 L of i-PrOH and dissolved by heating to reflux. After allowing to cool to room temperature, the salt was collected after 16 hours. A small sample of the salt was decomposed with aqueous acid and the free carboxylic acid was analyzed by chiral HPLC (Daicel ChiralPAK AD-H column, eluant: 0.1% TFA in 90:10 hexanes:i-PrOH) and was found to have 75% ee. The salt was re-suspended in 1.5 L of i-PrOH and dissolved by heating to reflux. After allowing to cool to room temperature, the salt was collected after 16 hours. This material was found to have 96% ee by chiral HPLC. This material was suspended in EtOAc (300 mL) and water (100 mL). Saturated aqueous KHSO4 (100 mL) was added with vigorous mixing. After two clear layers were obtained, the layers were separated, and the aqueous layer was extracted with EtOAc (100 mL). The combined extracts were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a light yellow oil which crystallized on drying in vacuo. Compound 1.4 was obtained as an off-white solid (23.5 g).

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