Hexane → (R)-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy)adenine

HRID 6267Notes

Reaction equation

HRID 6267 reaction equation
[Si]([O:18][CH2:19][C@@H:20]([O:33][CH2:34][P:35]([O:40][CH2:41][CH3:42])([O:37][CH2:38][CH3:39])=[O:36])[CH2:21][O:22][N:23]1[CH:31]=[N:30][C:29]2[C:24]1=[N:25][CH:26]=[N:27][C:28]=2[NH2:32])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC>FC(F)(F)C(O)=O.O>[CH2:41]([O:40][P:35]([CH2:34][O:33][C@H:20]([CH2:19][OH:18])[CH2:21][O:22][N:23]1[CH:31]=[N:30][C:29]2[C:24]1=[N:25][CH:26]=[N:27][C:28]=2[NH2:32])([O:37][CH2:38][CH3:39])=[O:36])[CH3:42]

Participants

4

Reactant 2

HCID 8058HexaneHCID 53833998(S)-9-[3-(t-Butyldiphenylsilyloxy)-2-(diethoxyphosphorylmethoxy)propoxy]adenine

Product 1

HCID 54312423(R)-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy)adenineYield 80%

Reagents, catalysts & solvents 1

HCID 22392675Trifluoroacetic acid waterSolvent

Procedure

(S)-9-[3-(t-Butyldiphenylsilyloxy)-2-(diethoxyphosphorylmethoxy)propoxy]adenine (0.61 g, 1 mmol) was dissolved in trifluoroacetic acid/water, 2:1 (6 ml) and the solution stirred at ambient temperature for 3 hours. Hexane (10 ml) was added and the mixture shaken. The aqueous phase was separated, washed once more with hexane (10 ml) and evaporated to dryness. The residue was treated with ethanolic ammonia solution (5 ml), at ambient temperature, for 5 minutes after which the solution was evaporated to dryness. The residue was chromatographed on silica gel using dichloromethane/methanol 90:10 as eluant to give (R)-9-[2-(diethoxyphosphorylmethoxy)-3-hydroxypropoxy]adenine as a colourless oil (0.3 g, 80%) which on prolonged standing, crystallised as white needles m.p. 98°-102°. IR: νmax (film) 3340, 3210, 2995, 2930, 2910, 1660, 1645, 1600, 1470, 1445, 1415, 1395, 1370, 1330, 1300, 1240, 1210, 1165, 1125, 1045. 1020, 980, 825, 95, 735 cm-1. 1H NMR: δH [(CD3)2SO] 1.23 (6H, t, J=7 Hz (OCH2CH3)2), 3.5-3.7 (2H, m, CH2OH), 3.75-3.85 (1H, m, CH), 3.95-4.15 (6H, m, (OCH2CH3)2, OCH2P), 4.38 (1H, dd, J=11.3 Hz, J=6.6 Hz, NOCHB), 4.55 (1H, dd, J= 11.3 Hz, J=3.0 Hz, NOCHA), 4.88 (1H, t, J=5.5 Hz, D2O exchangeable OH), 7.38 (2H, br.s., D2O exchangeable NH2), 8.15 (1H, s, H-2 or H-8), 8.43 (1H, s, H-2 or H-8). Found: C, 39.26; H, 6.05; N, 17.33%. C13H22N5O6P 1.25 H2O requires: C, 39.25; H, 6.20; N, 17 61%. m/z: (FAB, thioglycerol matrix) 376 (MH+).

Workup

  1. stirringthe mixture shaken
  2. customThe aqueous phase was separated
  3. washwashed once more with hexane (10 ml)
  4. customevaporated to dryness
  5. additionThe residue was treated with ethanolic ammonia solution (5 ml), at ambient temperature, for 5 minutes after which the solution
  6. customwas evaporated to dryness
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-582e76d720ad40bb92003abde5f4f836
Source dataset
uspto-grants-1993_09
Patent number
US05247085

Reaction notes

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