Water → 3-{3-[3-(2-Ethoxycarbonyl-2-methylpropyl)-benzoyl]phenyl}-2,2-dimethylpropionic acid ethyl ester

Under Ar atmosphere, to a solution of ethyl isobutyrate (59 g, 513 mmol) in THF (100 mL) was added LDA (256 mL, 2 M in heptanes, 512 mmol) at −78° C. The mixture was stirred for 30 min and a solution of bis-(3-bromomethylphenyl)-methanone (66.0 g, 179 mmol) in THF (100 mL) was added dropwise. The reaction mixture was allowed to stir overnight, gradually warming to room temperature. The mixture was hydrolyzed with ice (500 g) and water (800 g). The solution was extracted with MTBE (5×200 mL). The organic layers were washed with saturated NaHCO3 solution (100 mL) and saturated NaCl solution (100 mL), dried over MgSO4, and concentrated under vacuum. The residual oil (95 g) was subjected to column chromatography on silica (800 g) using hexanes/ethyl acetate (10:1) as eluent to afford 3-{3-[3-(2-ethoxycarbonyl-2-methylpropyl)-benzoyl]-phenyl}-2,2-dimethylpropionic acid ethyl ester (49.4 g, 63%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 7.67 (m, 2H), 7.59 (s, 2H), 7.40-7.38 (m, 4H), 4.11 (q, 4H, J=7.2 Hz), 2.96 (s, 4H), 1.23 (s, 12H), 1.22 (t, 6H, J=7.2 Hz). 13C NMR (75 MHz, CDCl3=77.00 ppm): δ (ppm): 196.6, 176.9, 138.2, 137.4, 134.1, 131.5, 128.3, 127.9, 60.4, 45.9, 43.5, 25.0, 14.1. HRMS (LSIMS, gly): Calcd for C27H35O5 (M+H): 439.2484, found: 439.2484.

1. stirringto stir overnight
2. extractionThe solution was extracted with MTBE (5×200 mL)
3. washThe organic layers were washed with saturated NaHCO3 solution (100 mL) and saturated NaCl solution (100 mL)
4. dry with materialdried over MgSO4
5. concentrationconcentrated under vacuum

ORD record

ord-1f922ac9306248e6be6dc604beed698a

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07335799B2