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

HRID 340975

반응식

HRID 340975 반응식
[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]

참가 물질

6

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-df3482bbd84f4c4682ed9f2168837b99
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895582B2

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