반응 #49222

반응 방정식

(2R,4R)-tert-butyl 2-((1S,2S)-2-amino-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate

3-bromo-5-(methoxycarbonyl)benzoic acid

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

Hunig's base

( 3 )

tert-butyl 3-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)morpholine-4-carboxylate

(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate

HATU

→

title compound

수율 79.0%

3-(dipropylcarbamoyl)benzoic acid

수율 79.0%

용매

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONwas then added
2. 2
   workup.STIRRINGthe reaction mixture was stirred at rt overnight
3. 3
   기타The crude mixture was purified by silica gel flash Chromatography (0% to 10% to 20% EtOAc/Hexane step gradient)

실험 절차

Step G (3): Preparation of (2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of 3-bromo-5-(methoxycarbonyl)benzoic acid (Step G (2), 111 mg, 0.43 mmol) in dichloromethane (10 mL) and was added Hunig's base (108 mg, 0.84 mmol) to make a clear solution and HATU (167 mg, 0.44 mmol) was then added. After stirring for 20 min, the reaction mixture was added (2R,4R)-tert-butyl 2-((1S,2S)-2-amino-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate (Example 1, Step 1 (A), 150 mg, 0.28 mmol) and the reaction mixture was stirred at rt overnight. The crude mixture was purified by silica gel flash Chromatography (0% to 10% to 20% EtOAc/Hexane step gradient) to give 170 mg of the title compound (79% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 0.03 (3H, s), 0.06 (3H, s), 0.83 (9H, s), 0.88 (3H, m), 1.45-1.54 (11H, m), 1.96-2.02 (1H, m), 2.20 (1H, d, J=10 Hz), 2.67 (1H, dd, J=5, 15 Hz), 2.84 (1H, m), 3.27-3.38 (3H, m), 3.76 (1H, dd, J=5, 10 Hz), 3.91 (3H, s), 4.00 (1H, m), 4.05-4.11 (2H, m), 4.63 (1H, m), 6.61 (1H, m), 6.76 (2H, d, J=5 Hz), 8.25 (1H, m), 8.32 (1H, s), 8.53 (1H, s), 8.74 (1H, d, J=5 Hz). MS (ESI) (M+H)+ 771.32.

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