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

HRID 47997

Reaction equation

HRID 47997 reaction equation
C([N-][CH:5]([CH3:7])[CH3:6])(C)C.[Li+].[C:9]([O:14][CH2:15][CH3:16])(=[O:13])[CH:10]([CH3:12])[CH3:11].Br[CH2:18][C:19]1[CH:20]=[C:21]([CH:32]=[CH:33][CH:34]=1)[C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]Br)[CH:25]=1)=[O:23].[CH3:35][O:36][CH2:37][C:38]1C=CC=C(Br)C=1.CN1C(=[O:52])N(C)CCC1>C1COCC1>[CH2:37]([O:36][C:35](=[O:52])[C:5]([CH3:6])([CH3:7])[CH2:18][C:19]1[CH:34]=[CH:33][CH:32]=[C:21]([C:22](=[O:23])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][C:10]([C:9]([O:14][CH2:15][CH3:16])=[O:13])([CH3:12])[CH3:11])[CH:25]=2)[CH:20]=1)[CH3:38]

Participants

7

Reactant 5

HCID 7342Ethyl isobutyrateHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 132195821-Bromo-3-(methoxymethyl)benzeneHCID 234315013,3'-Bis(bromomethyl)benzophenone

Product 1

HCID 112591923-{3-[3-(2-Ethoxycarbonyl-2-methylpropyl)-benzoyl]phenyl}-2,2-dimethylpropionic acid ethyl esterYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of lithium diisopropylamide (LDA, 2.0 M in heptane/THF, ethyl benzene, 42.2 mL, 84.4 mmol) was added drop-wise to a solution of ethyl isobutyrate (9.78 g, 84.3 mmol) in anhydrous THF (30 mL) at −78° C. The mixture was allowed to stir at −78° C. for 1 h, before 3,3′-bis(bromomethyl)benzophenone ((prepared according to Shultz, D. A.; Fox, M. A. J. Am. Chem. Soc. 1989, 16, 6311, from 3-bromobenzyl methyl ether (Friedman, L.; Shechter, H. J. Org. Chem. 1961, 26, 2522), 10.34 g, 28.1 mmol) was added, followed by addition of DMPU (2.7 g, 17 mmol). The mixture was stirred for 30 min at −78° C., allowed to warm to rt, and stirred for 30 min. The THF was removed under reduced pressure and the residue was diluted with saturated NH4Cl (280 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL), then dried over anhydrous Na2SO4 and concentrated in vacuo to furnish 3-{3-[3-(2-ethoxycarbonyl-2-methyl-propyl)-benzoyl]-phenyl}-2,2-dimethyl -prop ionic acid ethyl ester (11.0 g, 90%) as an oil. 1H NMR (300 MHz, CDCl3): δ (ppm): 7.8-7.2 (m, 8H), 3.98 (q, J=6.9 Hz, 4H), 2.83 (s, 4H), 1.2-0.8 (m, 18H). 13C NMR (75 MHz, CDCl3): δ (ppm): 196.5, 176.8, 138.1, 137.2, 134.0, 131.4, 128.1, 127.7, 60.3, 45.7, 43.3, 24.8, 13.9.

Workup

  1. customprepared
  2. temperatureto warm to rt
  3. stirringstirred for 30 min
  4. customThe THF was removed under reduced pressure
  5. additionthe residue was diluted with saturated NH4Cl (280 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  7. washThe combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee0e1af3855a43418ca96b7a18324cfc
Source dataset
uspto-grants-2004_03
Patent number
US06699910B2

Linked notes

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