Реакция #49223

Уравнение реакции

(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

potassium carbonate

trimethylboroxine

trimethylboroxine

trimethylboroxine

( 4 )

(2S,3S)-2-(3,5-difluorobenzyl)-3-(4-(tert-butoxycarbonyl)morpholin-3-yl)-3-hydroxypropanoic acid

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

→

title compound

Выход 77.0%

3-(dipropylcarbamoyl)benzoic acid

Выход 77.0%

Растворители

DMF

Ethyl acetate

Условия реакции

Обработка

1. 1
   Другоеwith sealed
2. 2
   Другоеcap for 5 h
3. 3
   workup.STIRRINGthe reaction was stirred at 60° C. overnight
4. 4
   workup.STIRRINGthe reaction was stirred at 100° C. for 6 h
5. 5
   Промывкаthe mixture was washed with H2O
6. 6
   Концентрированиеconcentrated under vacuum
7. 7
   ДругоеThe crude mixture was purified by silica gel Flash Chromatography (0% to 5% to 10% to 15% EtOAc/Hexane step gradient)

Методика

Step G (4): Preparation of (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-(methoxycarbonyl)-5-methylbenzamido)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution 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 (Step G (3). 163 mg, 0.21 mmol) in DMF (10 mL) were added potassium carbonate (87 mg, 0.63 mmol), Pd(PPh3)4 (24 mg, 0.021 mmol), and trimethylboroxine (53 mg, 0.42 mmol) and the reaction mixture was stirred at 100° C. with sealed cap for 5 h. Then another portion of trimethylboroxine (53 mg, 0.42 mmol) was added and the reaction was stirred at 60° C. overnight. Another portion of trimethylboroxine (53 mg, 0.42 mmol) was added and the reaction was stirred at 100° C. for 6 h. Ethyl acetate (100 mL) was added and the mixture was washed with H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 5% to 10% to 15% EtOAc/Hexane step gradient) to give 110 mg of the title compound (77% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 0.02 (3H, s), 0.07 (3H, s), 0.85 (9H, s), 0.88 (3H, m), 1.45-1.52 (11H, m), 2.02-2.07 (1H, m), 2.20 (1H, d, J=15 Hz), 2.41 (3H, s), 2.66 (1H, dd, J=10, 15 Hz), 2.94 (1H, m), 3.28-3.37 (3H, m), 3.76 (1H, dd, J=5, 10 Hz), 3.90 (3H, s), 3.99 (1H, m), 4.07-4.13 (2H, m), 4.62 (1H, m), 6.59 (1H, m), 6.77 (1H, s), 6.79 (1H, s), 7.91 (1H, s), 7.94 (1H, s), 8.20 (1H, brd s), 8.34 (1H, s). MS (ESI) (M+H)+ 705.41.

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