2,2-Dimethoxypropane → ((3aR,4R,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

HRID 511563Notes

Reaction equation

HRID 511563 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H]2OC(OCC)[O:18][C@@H:14]2[C@@H:13](CO)[CH2:12]1.[CH3:24][O:25][C:26]([O:29][CH3:30])([CH3:28])[CH3:27].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:24]2[O:25][C:26]([CH3:28])([CH3:27])[O:29][C@@H:30]2[C@@H:13]([CH2:14][OH:18])[CH2:12]1

Participants

4

Reactant 3

HCID 64952,2-DimethoxypropaneHCID 521998p-Toluenesulfonic acid monohydrateHCID 86666106((3aR,4R,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2-ethoxytetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Product 1

HCID 10064860((3aR,4R,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Procedure

The above crude ((3aR,4R,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2-ethoxytetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol was taken up in 2,2-dimethoxypropane (214 mL, 1740 mmol) and treated with p-toluenesulfonic acid monohydrate (13.2 g, 69.5 mmol) to afford a brown oil partially suspended in a cloudy solution, which was stirred at rt for 1 h 20 min; HPLC/LC MS indicated complete conversion to the desired product. The reaction was quenched by the careful addition of sodium bicarbonate (8.76 g, 104 mmol) and a minimal amount of water. The volatiles were removed in vacuo and the remaining aqueous layer was diluted with water (100 mL) and extracted with CH2Cl2 (3×400 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford a brown oil. Purification by column chromatography (7×16 cm silica; 0-5% MeOH/CH2Cl2) afforded the title compound (8.30 g, 74% over 3 steps) as a yellow foam: MS (ESI+) for C14H17ClN4O3 m/z 325.1 (M+H)+; MS (ESI−) for C14H17ClN4O3 m/z 369.0 (M+HCO2)−; HPLC purity >95 area %.

Workup

  1. customto afford a brown oil

Sources & evidence

ORD record
ord-76465f859c38430ea42a29022d4c61a5
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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