Triphenylphosphine → (S)-2-[bis-(t-butoxycarbonyl)amino]-9-[3-(t-butyldiphenylsilyloxy)-2-(diethoxyphosphorylmethoxy)propoxy]-6-methoxypurine

HRID 6265Notes

Reaction equation

HRID 6265 reaction equation
[Si:1]([O:18][CH2:19][C@@H:20]([O:23][CH2:24][P:25](=[O:32])([O:29][CH2:30][CH3:31])[O:26][CH2:27][CH3:28])[CH2:21][OH:22])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:52]([O:56][C:57]([N:59]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[C:60]1[N:68]=[C:67]2[C:63]([N:64]=[CH:65][N:66]2O)=[C:62]([O:70][CH3:71])[N:61]=1)=[O:58])([CH3:55])([CH3:54])[CH3:53].N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:75]([O:74][C:72]([N:59]([C:57]([O:56][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:58])[C:60]1[N:68]=[C:67]2[C:63]([N:64]=[CH:65][N:66]2[O:22][CH2:21][C@H:20]([O:23][CH2:24][P:25]([O:26][CH2:27][CH3:28])([O:29][CH2:30][CH3:31])=[O:32])[CH2:19][O:18][Si:1]([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:62]([O:70][CH3:71])[N:61]=1)=[O:73])([CH3:78])([CH3:77])[CH3:76]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 145239662-[Bis-(t-butoxycarbonyl)amino]-9-hydroxy-6-methoxypurineHCID 54250790Diethyl (S)-[1-(t-butyldiphenylsilyloxymethyl)-2-hydroxyethoxy]methylphosphonate

Product 1

HCID 53786032(S)-2-[bis-(t-butoxycarbonyl)amino]-9-[3-(t-butyldiphenylsilyloxy)-2-(diethoxyphosphorylmethoxy)propoxy]-6-methoxypurineYield 32.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of diethyl (S)-[1-(t-butyldiphenylsilyloxymethyl)-2-hydroxyethoxy]methylphosphonate (540 mg, 1.12 mmol), triphenylphosphine (440 mg, 1.68 mmol) and 2-[bis-(t-butoxycarbonyl)amino]-9-hydroxy-6-methoxypurine (prepared as described in EF-A-319228) (428 mg, 1.12 mmol) in dry THF (20 ml), cooled in ice and under a nitrogen atmosphere, was added dropwise diethyl azodicarboxylate (0.27 ml, 1.68 mmol). Within five minutes complete dissolution had occurred and the ice bath was removed. After 1 hour, the solution was evaporated to dryness and the residue obtained chromatographed on silica gel (initial eluant hexane: ethyl acetate 2:1, then hexane:ethyl acetate in the proportions 1:1, 1:2, 1:3) to yield (S)-2-[bis-(t-butoxycarbonyl)amino]-9-[3-(t-butyldiphenylsilyloxy)-2-(diethoxyphosphorylmethoxy)propoxy]-6-methoxypurine as a colourless glass (310 mg, 32%). 1H NMR: δH [(CD3)2SO] 0.96 (9H, s, t-Bu), 1.18, 1.19 (2×3H, 2×t, J= 7 Hz, (OCH2CH3)2), 1.37 (18H, br.s, 2×t-Bu), 3.7-4.15 (12H, m, CHCH2, (OCH2CH3)2, OCH2P, OCH3), 4.45-4.70 (2H, m, NOCH2), 7.25-7.75 (10H, m, 2×Ph), 8.75 (1H, s, H-8). m/z: (FAB+ve ion, thioglycerol/HCl) 844 (MH+, 4%), 644 (100%).

Workup

  1. temperaturecooled in ice and under a nitrogen atmosphere
  2. dissolutionWithin five minutes complete dissolution
  3. customthe ice bath was removed
  4. customthe solution was evaporated to dryness
  5. customthe residue obtained
  6. customchromatographed on silica gel (initial eluant hexane: ethyl acetate 2:1

Sources & evidence

ORD record
ord-fb64a9eb03c842dabe15b47f3ffd28fe
Source dataset
uspto-grants-1993_09
Patent number
US05247085

Reaction notes

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