Reaction Steps
A solution of the 4-[(3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid methyl ester (from Example 7, 433 mg, 1.18 mmol) in DMSO (2 mL) was treated with KOH (1.5 mmol) at 0° C. and allowed to warm to ambient temperature over 1 h. The yellow solution was cooled again to 0° C. and treated with a solution of bromohexane (156 mL, 1.30 mmol) in DMSO (1 mL) and allowed to warm to ambient temperature and stirred for 10 h. The reaction was quenched with saturated aqueous NH4Cl. The aqueous solution was adjusted to pH=3 with 1M HCl and extracted with EtOAc, 3×. The organic layers were combined and washed with water (2×) and brine. The organic solution was dried (NaSO4), filtered, and concentrated. Purification by silica gel radial chromatography (20:1=hexane:Et2O) gave 4-[2-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid, 317 mg (62%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ8.14 (½ABq, J=8.4 Hz, 2H, ArH), 7.84 (½ABq, J=8.4 Hz, 2H, ArH), 7.47 (s, 1H, ArH), 6.81 (s, 1H, ArH), 3.80 (t, J=6.2 Hz, 2H, OCH2), 1.17 (m, 4H, 2CH2), 1.34 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.28 (s, 6H, 2CH3), 1.11 (m, 4H, 2CH2), 0.95 (m, 2H, CH2), 0.80 (t, J=7.1 Hz, 3H, CH3). The hexyloxyketo acid (87 mg, 0.19 mmol) in EtOH (2 mL) was converted into the oxime derivative as described in Example 4 to provide, after recrysallization (CH2Cl2/hexanes), 4-[(3-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid oxime (114), 312 mg (60%) as a white solid: mp 197-199° C. (d); 1H NMR (400 MHz, CDCl3) δ8.14 (½ABq, J=8.5 Hz, 2H, ArH), 7.57 (½ABq, J=8.5 Hz, 2H, ArH), 7.22 (s, 1H, ArH), 6.85 (s, 1H, ArH), 3.82 (t, J=6.3 Hz, 2H, OCH2), 1.70 (m, 4H, 2CH2), 1.45 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.25 (s, 6H, 2CH3), 1.13 (m, 6H, 3CH2), 0.80 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ155.7, 153.8, 147.8, 141.1, 137.0, 130.3, 129.9, 128.4, 127.0, 118.5, 110.0, 68.3, 35.3, 35.0, 34.8, 33.8, 31.9, 31.8, 31.4, 29.0, 25.4, 22.5, 13.9.
