Acyclic retinoid

Potassium hydroxide (4.30 g) was dissolved in 2-propanol (40 mL) under nitrogen atmosphere, and the reaction solution was heated to 70° C., and then ethyl (2E, 4E, 6E, 10E)-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoate (17.0 g)/2-propanol (30 mL) was dropped thereto. After 15 minutes, the reaction solution was cooled to 0° C., and poured into cold water (70 mL). The reaction solution was washed with n-heptane (40 mL and 25 mL) sequentially, and the aqueous layer was pH-adjusted with diluted hydrochloric acid (26 mL), and then toluene (50 mL) was added thereto and an organic layer was extracted. The organic layer was washed with 5 mass percent sodium chloride solution (50 mL×twice), and concentrated under reduced pressure. When the distillation of toluene receded, methanol (20 mL) was added to the organic layer and concentrated under reduced pressure. Methanol (25 mL) was further added and dissolved, and the solution was cooled to crystallization. Once the internal temperature was elevated to 56° C., then the solution was cooled again to 0° C. to crystallization, and taken by filtration to give a wet crude crystal of (2E, 4E, 6E, 10E)-3, 7, 11, 15-tetramethylhexadeca-2, 4, 6, 10, 14-pentaenoic acid (9.07 g, 8.80 g in conversion to a dry crude crystal). [0151] (2E, 4E, 6E, 10E)-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoic acid (9.04 g wet crude crystal) was added to methanol (50 mL) under nitrogen atmosphere, and dissolved by heating to 60° C. This was filtered, and then cooled to crystallization. The precipitated crystal was taken by filtration to give (2E, 4E, 6E, 10E)-3, 7, 11, 15-tetramethylhexadeca-2, 4, 6, 10, 14-pentaenoic acid (8.15 g wet crystal). This was dried under reduced pressure to give a purified product of (2E, 4E, 6E, 10E)-3, 7, 11, 15-tetramethylhexadeca-2, 4, 6, 10, 14-pentaenoic acid (7.70 g). Residual TEPP was not recognized in this. [0152] 1H-NMR (CDPotassium hydroxide (30.00 g) was added to a three-necked flask equipped with a thermometer and a reflux condenser. 300 mL of isopropanol was added to the system, protected by nitrogen, and the temperature of the system was raised to 100 ° C. After the potassium hydroxide was completely dissolved, The above-mentioned pale yellow oily substance was resuscitretin (74.00 g) and maintained at reflux for 1 h.To the system, 300 mL of cold water and 300 mL of n-hexane.The resulting reaction solution was separated and the aqueous phase was adjusted to pH 6 to 7 with n-hexane (300 mL x 2) with 10percent dilute hydrochloric acid. The organic phases were washed with saturated ammonium chloride solution (200 mL x 2) and saturated brine (200 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 68.32 g of crude Ralei A acid and 98.5percent purity.