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

HRID 6266Notes

Reaction equation

HRID 6266 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:17]=[C:16]2[C:12]([N:13]=[CH:14][N:15]2[O:18][CH2:19][C@H:20]([O:40][CH2:41][P:42]([O:47][CH2:48][CH3:49])([O:44][CH2:45][CH3:46])=[O:43])[CH2:21][O:22][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)=[C:11]([O:50][CH3:51])[N:10]=1)=O)(C)(C)C>FC(F)(F)C(O)=O>[NH2:8][C:9]1[N:17]=[C:16]2[C:12]([N:13]=[CH:14][N:15]2[O:18][CH2:19][C@H:20]([O:40][CH2:41][P:42]([O:44][CH2:45][CH3:46])([O:47][CH2:48][CH3:49])=[O:43])[CH2:21][OH:22])=[C:11]([O:50][CH3:51])[N:10]=1

Participants

3

Reactant 1

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

Product 1

HCID 54289306(R)-2-amino-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]-6-methoxypurineYield 70%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (S)-2-[bis-(t-butyloxycarbonyl)amino]-9-[3-(t-butyldiphenylsilyloxy)-2-(diethoxyphosphorylmethoxy)propoxy]-6-methoxypurine (300 mg, 0.36 mmol) in 67% aqueous trifluoroacetic acid (3 ml) was kept at ambient temperature for 3 hours. The solution was washed with hexane (3×10 ml) and the aqueous phase evaporated to dryness. The residue obtained was chromatographed on silica gel (dichloromethane: methanol 95:5 as eluant, then 90:10) to give (R)-2-amino-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]-6-methoxypurine as a pale yellow glass (101 mg, 70%). 1H NMR: δH [(CD3)2SO] 1.23 (6H, t, J=7.1 Hz, (OCH2CH3)2), 3.5-3.65 (2H, m, CH2), 3.70-3.80 (1H, m, CH), 3.96 (3H, s, OCH3), 3.98-4.10 (6H, m, (OCH2CH3)2, OCH2P), 4.31 (1H, dd, J=11.27 Hz, J=6.87 Hz, NOCHB), 4.45 (1H, dd, J=11.27 Hz, J=3.02 Hz, NOCHA), 4.85 (1H, t, J=5.50 Hz, D2O exchangeable OH), 6.60 (2H, s, D2O exchangeable NH2), 8.14 (1H, s, H-8). m/z: (FAB+ve ion, thioglycerol) 406 (MH+, 100%).

Workup

  1. washThe solution was washed with hexane (3×10 ml)
  2. customthe aqueous phase evaporated to dryness
  3. customThe residue obtained
  4. customwas chromatographed on silica gel (dichloromethane: methanol 95:5 as eluant

Sources & evidence

ORD record
ord-3adadfaf6a7e475a88305c15d84145c4
Source dataset
uspto-grants-1993_09
Patent number
US05247085

Reaction notes

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