Tetrahydrofuran → 2-[Bis(t-butoxycarbonyl)amino]-9-[1-(t-butyldimethylsilyloxy)-4-(diethoxyphosphorylmethoxy)but-2-oxy]-6-methoxypurine

HRID 345070Notes

Reaction equation

HRID 345070 reaction equation
[Si:1]([O:8][CH2:9][CH:10]([OH:23])[CH2:11][CH2:12][O:13][CH2:14][P:15](=[O:22])([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(OC(N[C:32]1[N:33](O)[C:34]2[C:39]([N:40]=1)=[C:38]([O:41][CH3:42])[N:37]=[C:36]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[N:35]=2)=O)(C)(C)C.C1(P([C:65]2[CH:70]=[CH:69]C=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=N[C:73]([O:75]CC)=[O:74].O1CCC[CH2:84]1>>[C:70]([O:75][C:73]([N:43]([C:44]([O:46][C:47]([CH3:49])([CH3:48])[CH3:50])=[O:45])[C:36]1[N:35]=[C:34]2[C:39]([N:40]=[CH:32][N:33]2[O:23][CH:10]([CH2:11][CH2:12][O:13][CH2:14][P:15]([O:19][CH2:20][CH3:21])([O:16][CH2:17][CH3:18])=[O:22])[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[C:38]([O:41][CH3:42])[N:37]=1)=[O:74])([CH3:69])([CH3:65])[CH3:84]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 19993524Diethyl 4-t-butyldimethylsilyloxy-3-hydroxybutoxymethylphosphonateHCID 131717026Bis(t-butoxycarbonylamino]-9-hydroxy-6-methoxypurine

Product 1

HCID 199935582-[Bis(t-butoxycarbonyl)amino]-9-[1-(t-butyldimethylsilyloxy)-4-(diethoxyphosphorylmethoxy)but-2-oxy]-6-methoxypurineYield 47%

Conditions

Temperature
20 °C

Procedure

A solution of diethyl 4-t-butyldimethylsilyloxy -3-hydroxybutoxymethylphosphonate (0.49 g, 1.31 mmol), 2-[bis(t-butoxycarbonylamino]-9-hydroxy-6-methoxypurine (0.5 g, 1.31 mmol) and triphenylphosphine (0.52 g, 19.7 mmol) in tetrahydrofuran (50 ml) was cooled to 0° C. and treated with diethyl azodicarboxylate (0.31 ml, 1.97 mmol) before stirring for 4 h at 20° C. under nitrogen. The solution was evaporated in vacuo and the residue chromatographed twice on silica, eluting with chloroform-methanol 100:1 and then dichloromethanemethanol 200:1, affording 2-[bis(t-butoxycarbonyl)amino]-9-[1-(t-butyldimethylsilyloxy)-4-(diethoxyphosphorylmethoxy)but-2-oxy]-6-methoxypurine (0.45 g, 47%) as a clear oil. νmax (film) 3450, 1790, 1750, 1600, 1470, 1440 and 1390 cm-1 ; δH (CDCl3) 0.05 (6H, s, Si(CH3)2), 0.83 (9H, s, (CH3)3CSi), 1.27 (6H, t, J6.9 Hz, 2×CH2CH3), 1.40 (18H, s, 2×(CH3)3CN), 2.01 (2H, m, PCH2OCH2CH2), 3.74 (6H, m, CH2OCH2P+CH20Si), 4.09 (7H, m, 2×CH2CH3 +OCH3), 4.50 (1H, m, CHCH2Si), 8.10 (1H, s, H-8). Found: C, 50.54; H, 7.66; N, 9.38%; C31H56N5O11PSi requires C, 50.74; H, 7.69; N, 9.54%.

Workup

  1. customThe solution was evaporated in vacuo
  2. customthe residue chromatographed twice on silica
  3. washeluting with chloroform-methanol 100:1

Sources & evidence

ORD record
ord-d4d83b97378841bd8e98db641934e39c
Source dataset
uspto-grants-1991_10
Patent number
US05055458

Reaction notes

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