m-Chloroperbenzoic acid → (s)-Di-tert-butyl 5-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentyl phosphate

HRID 416408

Reaktionsgleichung

Reaktionsgleichung von HRID 416408
[Si:1]([O:8][CH2:9][C@@H:10]([N:15]([CH3:28])[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:21]=1[F:27])=[O:17])[CH2:11][CH2:12][CH2:13][OH:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si]([O:36]C(CC(N(C)C(NCC1C=CC=C(F)C=1F)=O)C)C([O-])=O)(C(C)(C)C)(C)C.N1C=NN=N1.C(N(C(C)C)[P:67]([O:73][C:74]([CH3:77])([CH3:76])[CH3:75])[O:68][C:69]([CH3:72])([CH3:71])[CH3:70])(C)C.C1C=C(Cl)C=C(C(OO)=O)C=1>C1COCC1>[P:67]([O:14][CH2:13][CH2:12][CH2:11][C@H:10]([N:15]([CH3:28])[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:21]=1[F:27])=[O:17])[CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3])([O:68][C:69]([CH3:70])([CH3:71])[CH3:72])([O:73][C:74]([CH3:75])([CH3:76])[CH3:77])=[O:36]

Komponenten

6

Edukt 4

HCID 70297m-Chloroperbenzoic acidHCID 853005Di-tert-butyl N,N-DiisopropylphosphoramiditeHCID 131729340(S)-1-(1-(tert-butyldimethylsilyloxy)-5-hydroxypentan-2-yl)-3-(2,3-difluorobenzyl)-1-methylurea (tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentanoateHCID 178418441HCID 178418441, Verbindung

Produkt 1

HCID 57947500(s)-Di-tert-butyl 5-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentyl phosphateAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (S)-1-(1-(tert-butyldimethylsilyloxy)-5-hydroxypentan-2-yl)-3-(2,3-difluorobenzyl)-1-methylurea-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentanoate (6.1 g, 14.66 mmol) in THF (20 mL) was added tetrazole (0.34 M in acetonitrile, 172.0 mL, 58.64 mmol) followed by addition of di-tert-butyl diisopropylphosphoramidite (9.3 mL, 29.32 mmol) at RT The resulting solution was stirred at RT for 2 h. To this mixture was added MCPBA (70%, 7.3 g, 29.32 mmol) at RT. The reaction mixture was stirred at RT overnight and quenched with Na2SO3. The mixture was filtered and the filtrate was concentrated and dissolved in EtOAc. The organic mixture was washed with NaOH (1N×2), NaHCO3 (sat.), and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-di-tert-butyl 5-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentyl phosphate (4.1 g, 54%). LRMS (M+H+−2 tBu) m/z 491.2.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at RT overnight
  2. customquenched with Na2SO3
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated
  5. dissolutiondissolved in EtOAc
  6. washThe organic mixture was washed with NaOH (1N×2), NaHCO3 (sat.), and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on silica gel column
  11. additiona mixture of EtOAc and hexanes

Quellen und Nachweise

ORD-Eintrag
ord-bd99809860e042dfb1ffe8ada8739506
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088793B2

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