Pyridine → benzyl (1-(5-(4-((1R,2S)-1-((bis(benzyloxy)-phosphoryl)oxy)-2-(2,2-difluoroacetamido)-3-fluoropropyl)phenyl)pyridin-2-yl)ethyl)carbamate

HRID 1520549Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1520549
FC(F)(F)C(O)=[O:4].[F:8][CH:9]([F:43])[C:10]([NH:12][C@H:13]([CH2:41][F:42])[C@@H:14]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH3:29])=[N:26][CH:27]=2)=[CH:18][CH:17]=1)[OH:15])=[O:11].N1C=CC=CC=1.C1COCC1.[CH2:55]([O:62][P:63]([O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)N(C(C)C)C(C)C)[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1.OO.O.S(=O)(=O)(O)[O-].[Na+]>O>[CH2:72]([O:71][P:63]([O:15][C@H:14]([C:16]1[CH:17]=[CH:18][C:19]([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH3:29])=[N:26][CH:27]=2)=[CH:20][CH:21]=1)[C@H:13]([NH:12][C:10](=[O:11])[CH:9]([F:8])[F:43])[CH2:41][F:42])([O:62][CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)=[O:4])[C:73]1[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=1

Komponenten

9

Edukt 7

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 449047Hydrogen peroxide waterHCID 516919Sodium BisulfateHCID 86695504benzyl (1-(5-(4-((1R,2S)-2-(2,2-difluoroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)pyridin-2-yl)ethyl)carbamate

Produkt 1

HCID 86695505benzyl (1-(5-(4-((1R,2S)-1-((bis(benzyloxy)-phosphoryl)oxy)-2-(2,2-difluoroacetamido)-3-fluoropropyl)phenyl)pyridin-2-yl)ethyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

Trifluoroacetic acid (51.6 μL) is added to the product of step 3, Example 95A (0.168 g, 0.335 mmol) and pyridine (54.2 μL, 0.67 mmol) in THF (4.4 mL, 54 mmol) at 0° C. After 5 minutes, bis(benzyloxy)(diisopropylamino)phosphine (0.219 mL, 0.586 mmol) is added. After allowing to warm to room temperature the mixture is stirred for 1 hour. 30% hydrogen peroxide/water (30:70, 60 μL, 0.586 mmol) is added. After 1 hour sodium bisulfate (4 mL) is added and water (10 mL) is added. The reaction mixture is extracted with ethylacetate (2×15 mL). The combined organics are dried over MgSO4, filtered and evaporated to give the crude product, which is purified by silica chromatography eluting from 25% ethylacetate/heptanes to neat ethylacetate to give the title product (241 mg): m/z: 761.25.

Aufarbeitung

  1. extractionThe reaction mixture is extracted with ethylacetate (2×15 mL)
  2. dry with materialThe combined organics are dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto give the crude product, which
  6. customis purified by silica chromatography
  7. washeluting from 25% ethylacetate/heptanes to neat ethylacetate

Quellen und Nachweise

ORD-Eintrag
ord-f81b824cc69646658d885e31e4021d94
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073894B2

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