Uridine → 1-[(6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]pyrimidine-2,4-dione

HRID 1028337

Reaktionsgleichung

Reaktionsgleichung von HRID 1028337
[C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].Cl[Si:19]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[O:20][Si:21](Cl)([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23]>N1C=CC=CC=1>[OH:3][C@@H:2]1[C@@H:4]2[O:5][Si:19]([CH:29]([CH3:31])[CH3:30])([CH:32]([CH3:34])[CH3:33])[O:20][Si:21]([CH:25]([CH3:27])[CH3:26])([CH:22]([CH3:23])[CH3:24])[O:8][CH2:7][C@H:6]2[O:9][C@H:1]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[O:12]

Komponenten

4

Edukt 2

HCID 6029UridineHCID 1724041,3-Dichlorotetraisopropyldisiloxane

Produkt 1

HCID 104805851-[(6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]pyrimidine-2,4-dioneAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel2×

Versuchsvorschrift

Uridine (15, 100.0 g, 409.5 mmol) was co-evaporated to dryness with anhydrous pyridine (600 mL) and re-suspended in anhydrous pyridine (700 mL). To this stirred fine suspension was added 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (135.7 g, 482.5 mmol) over 60 min at ambient temperature. After stirring the fine suspension for 17 h at ambient temperature, the reaction was quenched by adding methanol (20 mL) and then concentrated under reduced pressure. The residue was partitioned between ethyl acetate (1.5 L) and water (2 L). The organic layer was further washed with 5% hydrochloric acid (2×1 L), brine (500 mL), dried over solid sodium sulfate (50 g), filtered and concentrated under reduced pressure to the crude product, ca 250 g. The residue was subjected to a filtration column using silica gel (1.75 kg) and a gradient of ethyl acetate in hexanes 20-65%. The pure product fractions as judged by a homogenous TLC (Rf 0.55 in 1:1 hexanes-ethyl acetate) were combined and concentrated under reduced pressure and dried (40° C., 0.2 mm Hg, 24 h) to afford 145.5 g (76%) of 16 as a white foam solid. An additional fraction (35 g) of slightly impure 16 was also collected. 1H NMR (DMSO-d6) δ (ppm) 11.35 (s, 1H, NH), 7.66 (d, 1H, J=7.6 Hz, H-6), 5.57 (d, 1H, J=4.8 Hz, 2′-OH), 5.50-5.49 (m, 2H, 1′-H and H-5), 4.14-4.18 (m, 3H, 2′, 3′, 4′-H), 3.97-3.87 (m, 2H, 5′-Ha and Hb), 1.02-0.95 (m, 28H, CH(CH3)2).

Aufarbeitung

  1. customthe reaction was quenched
  2. additionby adding methanol (20 mL)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate (1.5 L) and water (2 L)
  5. washThe organic layer was further washed with 5% hydrochloric acid (2×1 L), brine (500 mL)
  6. dry with materialdried over solid sodium sulfate (50 g)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure to the crude product, ca 250 g
  9. filtrationThe residue was subjected to a filtration column
  10. concentrationconcentrated under reduced pressure
  11. customdried (40° C., 0.2 mm Hg, 24 h)

Quellen und Nachweise

ORD-Eintrag
ord-ad9ac7f774d14982bc685e0b8ab8b196
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735569B2

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