Acetic Acid → n2-Isobutyryl-9-(3',5'-di-o-[tetrahydropyran-2-yl]-beta-d-arabinofuranosyl)guanine

HRID 1865815Notes

Reaction equation

HRID 1865815 reaction equation
[C:1]([NH:6][C:7]1[NH:8][C:9](=[O:42])[C:10]2[N:11]=[CH:12][N:13]([C@@H:16]3[O:28][C@H:27]([CH2:29][O:30][C:31]4(C(=O)C(C)C)[CH2:36][CH2:35][CH2:34][CH2:33][O:32]4)[C@@H:19]([O:20][CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][O:22]4)[C@@H:17]3[OH:18])[C:14]=2[N:15]=1)(=[O:5])[CH:2]([CH3:4])[CH3:3].[OH-].[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+]>N1C=CC=CC=1.CO.O.CCO.CO>[C:1]([NH:6][C:7]1[NH:8][C:9](=[O:42])[C:10]2[N:11]=[CH:12][N:13]([C@@H:16]3[O:28][C@H:27]([CH2:29][O:30][CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][O:32]4)[C@@H:19]([O:20][CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][O:22]4)[C@@H:17]3[OH:18])[C:14]=2[N:15]=1)(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 137231693n2-Isobutyryl-9-(2'-isobutyryl-3',5'-di-o-[tetra-hydropyran-2-yl]-beta-d-arabinofuranosyl)guanine

Product 1

HCID 135514640n2-Isobutyryl-9-(3',5'-di-o-[tetrahydropyran-2-yl]-beta-d-arabinofuranosyl)guanineYield 78.3%

Reagents, catalysts & solvents 2

HCID 18681192Ethanol, mixt. with methanolSolventHCID 21976680Pyridine methanol waterSolvent

Conditions

Temperature
0 °C

Procedure

N2-Isobutyryl-9-(2′-isobutyryl-3′,5′-di-O-[tetra-hydropyran-2-yl]-β-D-arabinofuranosyl)guanine (5.58 g) was dissolved in pyridine-MeOH-H2O (65:30:15, 52 mL) at room temperature. The solution was cooled to 0° C. and 52 mL of 2 N NaOH in EtOH-MeOH (95:5) was added slowly, followed by stirring for 2 hours at 0° C. Glacial acetic acid was added to pH 6, and saturated NaHCO3 was added to pH 7. The reaction mixture was evaporated under reduced pressure and the residue coevaporated with toluene. The residue was then dissolved in EtOAc (150 mL) and washed 3× with saturated NaHCO3. The organic phase was evaporated and the residue purified by silica gel column chromatography using EtOAc-MeOH (95:5) as the eluent, yielding 3.85 g (78.3%) of product.

Workup

  1. additionwas added to pH 7
  2. customThe reaction mixture was evaporated under reduced pressure
  3. dissolutionThe residue was then dissolved in EtOAc (150 mL)
  4. washwashed 3× with saturated NaHCO3
  5. customThe organic phase was evaporated
  6. customthe residue purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9bffe6e9e5bc414a95d27bd6c8f7ac1c
Source dataset
uspto-grants-2009_12
Patent number
US07629321B2

Reaction notes

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