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

HRID 340975

Reaction equation

HRID 340975 reaction equation
[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]

Participants

6

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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 (1 N×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.

Workup

  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 (1 N×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

Sources & evidence

ORD record
ord-df3482bbd84f4c4682ed9f2168837b99
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Linked notes

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