Reaktion #2448775

Reaktionsgleichung

t-BuOK

(2S,4R)-1-((3R)-2-((tert-butoxycarbonyl)amino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid

1-chloro-4-methoxyisoquinoline

→

desired product

Ausbeute 40.0%

(2S,4R)-1-((2S,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-(4-methoxyisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid

Ausbeute 40.0%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mass was quenched with aqueous citric acid solution
2. 2
   Extraktionextracted with ethyl acetate
3. 3
   TrocknenThe combined organic layer was dried over anhydrous Na2SO4
4. 4
   Einengenconcentrated under reduced pressure
5. 5
   Sonstigeto get crude compound
6. 6
   SonstigeThe crude compound was purified by combiflash

Vorschrift

To a solution of (2S,4R)-1-((3R)-2-((tert-butoxycarbonyl)amino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid (1.5 g, 3.6 mmol) in DMSO was added 1-chloro-4-methoxyisoquinoline (840 mg, 4.4 mmol) followed by t-BuOK (1M sol. in THF, 18 mL) at room temperature under nitrogen atmosphere. The reaction mass was stirred at room temperature for 4 h. The reaction mass was quenched with aqueous citric acid solution and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get crude compound. The crude compound was purified by combiflash to get desired product (800 mg, 40%) as off-white solid. 1H NMR (400 MHz, CDCl3): δ ppm 8.11-8.09 (m, 2H), 7.70-7.66 (t, J=7.4 Hz, 1H), 7.56-7.51 (t, J=8.0 Hz, 1H), 7.47 (s, 1H), 5.78 (bs, 1H), 5.69-5.65 (m, 1H), 5.14-5.11 (m, 1H), 4.96-4.88 (m, 3H), 4.43-4.41 (m, 1H), 4.27-4.24 (m, 1H), 3.99 (s, 4H), 2.75-2.73 (m, 1H), 2.67-2.65 (m, 1H), 2.10 (bs, 1H), 1.88-1.85 (m, 2H), 1.31 (s, 9H), 1.24 (s, 2H), 0.98-0.96 (m, 4H), 0.91-0.86 (m, 4H) MS: MS m/z 568.2 (M++1).

Quelle