(1R,6S)-2,2,6-trimethylcyclohexane-1-carbaldehyde

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude product of Example 3a (6.36 g, 32.4 mmol) in toluene (11 mL) (15.7 g) was added 85% phosphoric acid (12 mL). The mixture was heated to 100° C. for 4 hours. The reaction mixture was cooled to room temperature and toluene (12 mL) along with water (24 mL) was added and the layers were separated. The aqueous layer was extracted with toluene (12 mL×2). The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 mL×2) and brine (50 mL×2). Concentration and distillation under reduced pressure (b.p. 65-70° C.) afforded the title compound as a 9:1 mixture of epimers as a colorless oil (2.51 g, Yield: 50%). 1H NMR (400 MHz, CDCl3) (Major) δ 9.63 (d, J=5.2 Hz, 1H), 2.03-1.91 (m, 1H), 1.83-1.75 (m, 1H), 1.64-1.60 (m, 1H), 1.54-1.48 (m, 1H), 1.40-1.35 (m, 1H), 1.24-1.14 (m, 1H), 1.02 (s, 3H), 0.97 (s, 3H), 0.95-0.84 (m, 2H), 0.81 (d, J=6.4 Hz, 3H) ppm. [α]D24=+5.20° (c=1.00, dichloromethane). The reaction mixture was cooled to room temperature the layers were separated The aqueous layer was extracted with toluene (12 mL×2) The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 mL×2) and brine (50 mL×2) Concentration and distillation under reduced pressure (b.p. 65-70° C.)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude product of Example 1a (6.36 g, 32.4 mmol) in toluene (11 mL) (15.7 g) was added 85% phosphoric acid (12 mL). The mixture was heated to 100° C. for 4 hours. The reaction mixture was cooled to room temperature and toluene (12 mL) along with water (24 mL) was added and the layers were separated. The aqueous layer was extracted with toluene (12 mL×2). The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 mL×2) and brine (50 mL×2). Concentration and distillation under reduced pressure (b.p. 65-70° C.) afforded the title compound as a 9:1 mixture of epimers as a colorless oil (2.51 g, Yield: 50%). 1H NMR (400 MHz, CDCl3) (Major) δ 9.63 (d, J=5.2 Hz, 1H), 2.03-1.91 (m, 1H), 1.83-1.75 (m, 1H), 1.64-1.60 (m, 1H), 1.54-1.48 (m, 1H), 1.40-1.35 (m, 1H), 1.24-1.14 (m, 1H), 1.02 (s, 3H), 0.97 (s, 3H), 0.95-0.84 (m, 2H), 0.81 (d, J=6.4 Hz, 3H) ppm. [α]D24=+5.20° (c=1.00, dichloromethane). The reaction mixture was cooled to room temperature the layers were separated The aqueous layer was extracted with toluene (12 mL×2) The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 mL×2) and brine (50 mL×2) Concentration and distillation under reduced pressure (b.p. 65-70° C.)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 300-ml 4-necked flask equipped with a condenser, a thermometer, a dropping funnel, and a stirrer was placed 42 g of nitric acid (aqueous 60% solution), and the temperature was raised to 55° C. by heating. To the solution was added dropwise 100 g (0.65 mole) of (1R,6S)-2,2,6-trimethylcyclohexanecarbaldehyde (10) [composition: 90% of the (1R,6S)-form, 10% of the (1S,6S)-form] synthesized in Synthetic Example 4-A) with stirring over a period of 2 hours. After carrying out the reaction for 3 hours at the same temperature, the reaction mixture was washed with water with 100 g of toluene and 100 g of water at room temperature, followed by separating an organic layer from an aqueous layer. The organic layer was washed thrice with 100 g of a saturated aqueous sodium chloride solution, followed by separating the organic layer from an aqueous layer. The toluene was distilled off from the organic layer by an evaporator under reduced pressure to provide 109 g of crude (1R,6S)-2,2,6-trimethylcyclohexanecarboxylic acid (11) [composition: 91% of the (1R,6S)-form, 9% of the (1S,6S)-form; melting point: 44° C. to 54° C⟧ In a 300-ml 4-necked flask equipped with a condenser by heating 90% of the (1R,6S)-form, 10% of the (1S,6S)-form] synthesized in Synthetic Example 4-A) the reaction for 3 hours at the same temperature the reaction mixture was washed with water with 100 g of toluene and 100 g of water at room temperature by separating an organic layer from an aqueous layer The organic layer was washed thrice with 100 g of a saturated aqueous sodium chloride solution by separating the organic layer from an aqueous layer The toluene was distilled off from the organic layer by an evaporator under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of crude product of Example 3a (6.36 g, 32.4 mmol) in toluene (11 mL) (15.7 g) was added 85% phosphoric acid (12 mL). The mixture was heated to 100° C. for 4 hours. The reaction mixture was cooled to room temperature and toluene (12 mL) along with water (24 mL) was added and the layers were separated. The aqueous layer was extracted with toluene (12 mL×2). The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 mL×2) and brine (50 mL×2). Concentration and distillation under reduced pressure (b.p. 65-70° C.) afforded the title compound as a 9:1 mixture of epimers as a colorless oil (2.51 g, Yield: 50%). 1H NMR (400 MHz, CDCl3) (Major) δ 9.63 (d, J=5.2 Hz, 1H), 2.03-1.91 (m, 1H), 1.83-1.75 (m, 1H), 1.64-1.60 (m, 1H), 1.54-1.48 (m, 1H), 1.40-1.35 (m, 1H), 1.24-1.14 (m, 1H), 1.02 (s, 3H), 0.97 (s, 3H), 0.95-0.84 (m, 2H), 0.81 (d, J=6.4 Hz, 3H) ppm. [α]D24=+5.20° (c=1.00, dichloromethane). The reaction mixture was cooled to room temperature the layers were separated The aqueous layer was extracted with toluene (12 mL×2) The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 mL×2) and brine (50 mL×2) Concentration and distillation under reduced pressure (b.p. 65-70° C.)