Synthetic Route of 136333-97-6, A common heterocyclic compound, 136333-97-6, name is Methyl 4-(2-bromoethyl)benzoate, molecular formula is C10H11BrO2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
[0487] Scheme 3 , Step I: Preparation of (i?)-methyl 4-(2-(5 -(((tert- butyldimethylsilyl)oxy)methyl)-3 ,3 -difluoro-2-oxopyrrolidin- 1 -yl)ethyl)benzoate (lib; PG=TBS) [0488] To a suspension consisting of sodium hydride (60% in mineral oil, 61 mg, 1.5 mmol) and sodium iodide (251 mg, 1.67 mmol) in DMF (40 mL) was added dropwise a solution consisting of (i?)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3,3-difluoropyrrolidin-2- one (intermediate 9; PG=TBS, 370 mg, 1.39 mmol) in DMF (5 mL). The mixture was stirred at room temperature for two hours followed by 50C for 30 minutes. To the reaction mixture was added dropwise methyl 4-(2-bromoethyl)benzoate (406 mg, 1.67 mmol) in DMF (5 mL), and stirring continued overnight at 50C. The mixture was diluted with ethyl acetate and washed sequentially with 0.5 N hydrochloric acid, a 5% aqueous solution of sodium thiosulfate, 50% brine, and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography. Elution with ethyl acetate :heptane (increasing solvent strength, 1 :50 v/v to 1 : 10 v/v) followed by eluting with methanol-dichloromethane (1 :50 v/v) afforded the title intermediate (39 mg, 6.6%); TLC R/ 0.6 (solvent system: 70:30 v/v heptane:ethyl acetate); -NMR (CDC13) delta 7.9 (d, 2H), 7.28 (d, 2H), 3.98-3.91 (m, 1H), 3.9 (s, 3H), 3.74-3.48 (m, 2H), 3.46-3.35 (m, 2H), 3.1-2.9 (m, 2H), 2.48-2.18 (m, 2H), 0.8 (s, 9H), 0.0 (s, 6H); MS (ESf ) m/z 445.1 (M+NH3). [0489] Significant improvement of the yield (in relation to (R)-5-(((tert- butyldimethylsilyl)oxy)methyl)-3,3-difluoropyrrolidin-2-one) was realized by repeated additions of sodium hydride and methyl 4-(2-bromoethyl)benzoate to the reaction mixture.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; CAYMAN CHEMICAL COMPANY, INC.; MYOMETRICS, LLC; BARRETT, Stephen, Douglas; CISKE, Fred, Lawrence; COLOMBO, Joseph, Michael; ENDRES, Gregory, William; GERMAIN, Bradlee, David; KORNILOV, Andriy; KRAMER, James, Bernard; UZIEBLO, Adam; OWEN, Thomas, Allen; O’MALLEY, James, Paul; WO2014/15246; (2014); A1;,
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