반응 #49225

반응 방정식

(R)-2-(methoxymethyl)pyrrolidine

3-bromo-5-(methoxycarbonyl)benzoic acid

Hunig's base

( 1 )

(2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid

(R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate

HATU

→

title compound

수율 73.0%

3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acid

수율 73.0%

용매

dichloromethane

Dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONwas then added
2. 2
   workup.STIRRINGthe reaction mixture was stirred at rt for 6 h
3. 3
   세척the mixture was washed with 1N NaOH, H2O
4. 4
   농축concentrated under vacuum
5. 5
   기타The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient)

실험 절차

Step H (1): (R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate. To a solution of 3-bromo-5-(methoxycarbonyl)benzoic acid (1.8 g, 6.95 mmol) in dichloromethane (100 mL) and was added Hunig's base (2.7 g, 20.85 mmol) to make a clear solution and HATU (3.17 g, 8.34 mmol) was then added. After stirring for 30 min, the reaction mixture was added (R)-2-(methoxymethyl)pyrrolidine (800 mg, 6.95 mmol) and the reaction mixture was stirred at rt for 6 h. Dichloromethane (100 mL) was added and the mixture was washed with 1N NaOH, H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient) to give 1.8 g of the title compound (73% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 1.77-2.08 (4H, m), 3.14-3.47 (5H, m), 3.63 (2H, brd s), 3.82 (3H, s), 4.41 (1H, brd s), 7.83 (1H, s), 8.07 (1H, s), 8.20 (1H, m).

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