Reaktion #49250

Reaktionsgleichung

( D )

(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

compound

3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acid

methanol

ozone

(2R,4R)-tert-butyl 2-((1S,2S)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate

→

sulfone

Ausbeute 64.0%

N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide

Ausbeute 64.0%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction solution was partitioned between ethyl acetate and water
2. 2
   Einengenthe organic layer was concentrated
3. 3
   Sonstigethe crude product was purified by chromatography
4. 4
   Wascheneluting with a gradient of 20 to 80% ethyl acetate in hexanes

Vorschrift

Step 17 (D): (2R,4R)-tert-butyl 2-((1S,2S)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate. A solution of 130 mg (0.2 mmol) of the compound of step 17 (C) dissolved in 2 mL of methanol was treated with a solution of 240 mg (0.4 mmol) of ozone dissolved in 0.4 mL of water. After stirring at rt from 30 min, the reaction solution was partitioned between ethyl acetate and water, the organic layer was concentrated, and the crude product was purified by chromatography eluting with a gradient of 20 to 80% ethyl acetate in hexanes to provide 86 mg (64%) of the desired sulfone and 37 mg (28%) of the sulfoxide intermediate as a lower-eluting compound. 1H NMR (500 MHz, CDCl3) δ ppm 0.06 (s, 3H) 0.11 (s, 3H) 0.96 (s, 9H) 1.07 (t, J=7.32 Hz, 3H) 1.47 (s, 9H) 1.87 (dd, J=13.43, 6.71 Hz, 3H) 2.03 (s, 1H) 2.26 (t, J=12.21 Hz, 1H) 2.38 (s, 1H) 2.68 (s, 1H) 2.90 (s, 2H) 3.46 (m, 2H) 3.75 (s, 1H) 4.09 (m, 2H) 4.26 (d, J=7.02 Hz, 1H) 4.77 (m, 1H) 4.95 (m, 1H) 7.18 (m, 10H) MS (ESI) (M+H−Boc)+=575.25

Quelle