Pyridine → (2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxy-methyl]-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

HRID 1913049Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1913049
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([O:19][CH3:20])[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C@@H:10]([CH2:17][OH:18])[O:9]2)=[CH:4][C:3]=1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]([F:33])([F:32])[F:31])=[CH:24][CH:23]=1.[CH3:34][C:35]([Si:38](Cl)([CH3:40])[CH3:39])([CH3:37])[CH3:36].N1C=CC=CC=1>CN(C=O)C.CN(C1C=CN=CC=1)C>[Si:38]([O:18][CH2:17][C@H:10]1[O:9][C@:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]([F:33])([F:31])[F:32])=[CH:24][CH:23]=3)[CH:4]=2)([O:19][CH3:20])[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@@H:11]1[OH:16])([C:35]([CH3:37])([CH3:36])[CH3:34])([CH3:40])[CH3:39]

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 28928tert-Butyldimethylsilyl chlorideHCID 86685147(2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

Produkt 1

HCID 86685148(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxy-methyl]-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triolAusbeute 62,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 7e (3.8 g, 7.71 mmol) was dissolved in 100 mL DMF, followed by addition of DMAP (188 mg, 1.54 mmol), TBSCl (1.39 g, 9.25 mmol) and pyridine (50 mL) in turn, and the reaction mixture was stirred for 36 hours. Thereafter, the reaction mixture was concentrated under reduced pressure and partitioned after 150 mL water were added. The aqueous phase was extracted with ethyl acetate (100 mL×3) and the organic extract was washed with saturated sodium chloride solution (30 mL) and combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography with elution system D to obtain the title compound (2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxy-methyl]-2-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 7f (2.94 g, yellow grease), yield: 62.8%. 1H NMR (400 MHz, DMSO-d6): δ 7.94 (s, 2H), 7.45 (d, 1H), 7.40 (d, 1H), 7.35-7.28 (m, 1H), 7.17-7.05 (m, 2H), 7.01-6.90 (m, 2H), 5.00 (d, 1H), 4.84-4.74 (m, 2H), 4.68 (q, 2H), 4.11-3.87 (m, 3H), 3.73 (dd, 1H), 3.60-3.46 (m, 1H), 3.42 (ddd, 1H), 3.14 (td, 1H), 2.92 (s, 3H), 0.05-0.02 (m, 3H).

Aufarbeitung

  1. concentrationThereafter, the reaction mixture was concentrated under reduced pressure
  2. custompartitioned after 150 mL water
  3. additionwere added
  4. extractionThe aqueous phase was extracted with ethyl acetate (100 mL×3)
  5. extractionthe organic extract
  6. washwas washed with saturated sodium chloride solution (30 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe resulting residue was purified by silica gel chromatography with elution system D

Quellen und Nachweise

ORD-Eintrag
ord-b1a386e6cb1c460780920c2953067014
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609622B2

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