Butyl bromide → Methyl Benzoate

A solution of the 4-[(3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid methyl ester (433 mg, 1.18 mmol) in DMF (2 mL) was treated with NaH (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 bromobutane (119 mL, 1.30 mmol) in DMF (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 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 to give a colorless oil. Purification by silica gel flash chromatography (20:1=hexanes:Et2O) gave 4-[3-butyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid methyl ester 275 mg (55%) as a white solid: 1H NMR (400 MHz, CDCl3) δ8.07 (½ABq, J=8.2 Hz, 2H, ArH), 7.81 (½ABq, J=8.2 Hz, 2H, ArH), 7.44 (s, 1H, ArH), 6.82 (s, 1H, ArH), 3.95 (s, 3H, OCH3), 3.81 (t, J=6.2 Hz, 2H, OCH2), 1.70 (m, 4H, 2CH2), 1.34 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.27 (s, 6H, 2CH3), 1.02 (m, 2H, CH2), 0.71 (t, J=7.2 Hz, 3H, CH3); HRMS calcd. for C27H34O4 423.2535 (MH+), found 423.2505. The butyloxy keto ester (150 mg, 0.36 mmol) was hydrolyzed with excess KOH in MeOH as described in Example 1 to give 4-[(3-butyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid (111) 82 mg (59%) as a white solid: mp 207-210° C.; 1H NMR (400 MHz, CDCl3) δ8.14 (½ABq, J=8.2 Hz, 2H, ArH), 7.84 (½ABq, J=8.2 Hz, 2H, ArH), 7.46 (s, 1H, ArH), 6.82 (s, 1H, ArH), 3.81 (t, J=6.2 Hz, 2H, OCH2), 1.71 (m, 4H, 2CH2), 1.32 (s, 6H, 2CH3), 1.29 (m, 2H, CH2), 1.28 (s, 6H, 2CH3), 1.00 (m, 2H, CH2), 0.72 (t, J=7.3 Hz, 3H, CH3); HRMS calcd. for C26H32O4 408.2301 (M+), found 408.2300.

1. temperatureThe yellow solution was cooled again to 0° C.
2. temperatureto warm to ambient temperature
3. customThe reaction was quenched with saturated aqueous NH4Cl
4. extractionThe aqueous solution was extracted with EtOAc, 3×
5. washwashed with water (2×) and brine
6. dry with materialThe organic solution was dried (NaSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give a colorless oil
10. customPurification by silica gel flash chromatography (20:1=hexanes:Et2O)

ORD record

ord-5f70519c8c66409499b65475f72dec7a

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06545049B1