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 bromopropane (118 mL, 1.30 mmol) in DMSO (1mL) 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=hexanes:Et2O) gave 4-[2-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid 337 mg (75%) as a coloreless oil: 1H NMR (400 MHz, CDCl3) δ8.15 (½ABq, J=8.2 Hz, 2H, ArH), 7.85 (½ABq, J=8.2 Hz, 2H, ArH), 7.46 (s, 1H, ArH), 6.82 (s, 1H, ArH), 3.78 (t, J=6.3 Hz, 2H, OCH2), 1.70 (m, 4H, 2CH2), 1.36 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.28 (s, 6H, 2CH3), 0.62 (t, J=7.4 Hz, 3H, CH3). The propoxyketo acid (1.34 mg, 0.33 mmol) in EtOH (2mL) was converted to the oxime derivative as described in Example 4 to provide, after recrystallization (CH2Cl2/hexanes (4-[(3-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid oxime (109) (97%) as a white solid: mp 251-255° C. (d); 1H NMR (400 MHz, CDCl3) δ7.98 (½ABq, J=8.4 Hz, 2H, ArH), 7.54 (½ABq, J=8.4 Hz, 2H, ArH), 7.13 (s, 1H, ArH), 6.86 (s, 1H, ArH), 3.81 (t, J=6.2 Hz, 2H, OCH2), 1.70 (m, 4H, 2CH2), 1.51 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.24 (s, 6H, 2CH3), 0.72 (t, J=7.4 Hz, 3H, CH3).
