Methanol → 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

HRID 20972Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 20972
[Si](O[C@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)[C@@H:10]([NH:20][C:21](=[O:38])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([N:30]2[CH2:34][CH2:33][CH2:32][C@@H:31]2[CH2:35]OC)=[O:29])[CH:23]=1)[CH2:11]C1C=C(F)C=C(F)C=1)(C(C)(C)C)(C)C.C(OC([C@@H:65]([CH2:93][C:94]1[CH:99]=[CH:98][CH:97]=[CH:96][CH:95]=1)[C@@H:66]([C@H:75]1[CH2:79][C@@H:78]([S:80]([CH2:83][CH2:84][CH3:85])(=[O:82])=[O:81])[CH2:77][N:76]1C(OC(C)(C)C)=O)[O:67][Si](C(C)(C)C)(C)C)=O)C1C=CC=CC=1.C([O:104][C:105]([N:107]1C[C@H](OCCC)C[C@@H]1[C@@H](O[Si](C(C)(C)C)(C)C)[C@@H](NC(C1C=C(C=CC=1)C(O)=O)=O)CC1C=C(F)C=C(F)C=1)=O)(C)(C)C.O=[O+][O-].[CH3:150]O>O>[OH:67][C@H:66]([C@H:75]1[CH2:79][C@@H:78]([S:80]([CH2:83][CH2:84][CH3:85])(=[O:81])=[O:82])[CH2:77][NH:76]1)[C@@H:65]([NH:107][C:105](=[O:104])[C:26]1[CH:27]=[C:22]([C:21]2[O:38][CH:11]=[CH:10][N:20]=2)[CH:23]=[C:24]([C:28]([N:30]([CH2:31][CH2:35][CH3:150])[CH2:34][CH2:33][CH3:32])=[O:29])[CH:25]=1)[CH2:93][C:94]1[CH:95]=[CH:96][CH:97]=[CH:98][CH:99]=1

Komponenten

7

Edukt 5

HCID 887MethanolHCID 24823OzoneHCID 67315894(2r,4r)-Tert-butyl 2-((1s,2s)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylateHCID 673161403-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acidHCID 67316242(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

Produkt 1

HCID 11848640N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamideAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

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

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-70d510e877134b7ca2f0eeb9bf71ef49
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745470B2

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