Chlorotrimethylsilane → Methyl 3-(4-methylbenzamido)-4-oxopentanoate
Reaction equation
[CH3:1][O:2][C:3]([CH2:5][C@H:6]([NH2:10])[C:7]([OH:9])=O)=[O:4].Cl.[CH3:12]CN(CC)CC.[Si](Cl)(C)(C)C.[C:24]1([CH3:33])[CH:29]=[CH:28][C:27]([C:30](Cl)=[O:31])=[CH:26][CH:25]=1>C(Cl)Cl>[CH3:33][C:24]1[CH:29]=[CH:28][C:27]([C:30]([NH:10][CH:6]([C:7](=[O:9])[CH3:12])[CH2:5][C:3]([O:2][CH3:1])=[O:4])=[O:31])=[CH:26][CH:25]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
To a suspension of L-aspartic acid β-methyl ester hydrochloride (250 g, 1.36 mol) in chilled (<5° C.) CH2Cl2 (4 L) was added Et3N (440 g, 4.35 mol) in a steady flow followed by a slow addition of Me3SiCl (324 g, 2.99 mol). The mixture was warmed to 25° C. and stirred for one hour, cooled again (<10° C.), and p-toluoyl chloride (205 g, 1.36 mol) was added dropwise. The mixture was allowed to warm to ambient slowly with stirring for 16 hours. The reaction mixture was then diluted with CH2Cl2 (500 mL) and washed with 1N HCl (500 mL), brine (500 mL), and dried over Na2SO4. The resultant amide product (310 g, 91%), a white solid, was obtained after solvent removal and drying under vacuum. It was then dissolved in pyridine (1.25 L) and DMAP (5 g) was added. Acetic anhydride (840 mL) was added slowly and then the reaction was heated at 90° C. for 2 hours. The cooled solution was poured into 7 L ice water and extracted with 6 L EtOAc. The organic layer was washed with 2N HCl (3×1 L) and 1N NaOH (1 L), dried over MgSO4 and concentrated to afford the title compound as a white solid (301 g, 93%).
Workup
- additionwas added dropwise
- temperatureto warm to ambient slowly
- stirringwith stirring for 16 hours
- washwashed with 1N HCl (500 mL), brine (500 mL)
- dry with materialdried over Na2SO4
Sources & evidence
- ORD record
- ord-3c9c443695a5429b87f81fd52b3c3677
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07358386B2
Reaction notes
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