Diisopropylamine → 4-[2-(2-Bromo-5-methoxyphenyl)-1-methylethyl]benzoic acid
Reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH2:13]([C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=1)[CH3:14].[Br:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[CH2:33]Br>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[CH2:33][CH:13]([C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=1)[CH3:14]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -5 °C
Procedure
Butyl lithium (1.6M hexanes, 35 mL, 56 mmol) was added dropwise to a THF (50 mL)/HMPA (10 mL) solution of diisopropylamine (7.9 mL, 56 mmol) cooled to −5° C. After stirring 10 minutes a THF solution (17 mL) of 4-ethylbenzoic acid (3.36 g, 22.4 mmol) was added dropwise. The red solution was kept at 5° C. overnight. A THF solution (17 mL) of 1-bromo-2-(bromomethyl)-4-methoxybenzene (60.27 g, 22.4 mmol) was added dropwise. The reaction solution was then allowed to warm to room temperature. The solution was then partitioned between ethyl acetate and aqueous 1N HCl. The organic phase was washed with water, brine and dried over MgSO4. The filtered solution was concentrated and the residue purified by silica gel chromatography using hexanes/ethyl acetate (with 1% AcOH) gradient to give the title compound. LCMS1 3.72 min. (M−17)=331
Workup
- additionwas added dropwise
- temperatureto warm to room temperature
- customThe solution was then partitioned between ethyl acetate and aqueous 1N HCl
- washThe organic phase was washed with water, brine
- dry with materialdried over MgSO4
- concentrationThe filtered solution was concentrated
- customthe residue purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-e233e9b8eed742b1b2fa034ba04f7a45
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08318760B2
Reaction notes
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