Thymine → HCID 57867391, compound

HRID 1516288Notes

Reaction equation

HRID 1516288 reaction equation
[NH:1]1[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]1=[O:3].C(O[C@@H:14]1[C:18]([F:20])([CH3:19])[C@@:17]([O:22][C:23](=[O:25])[CH3:24])([CH3:21])[CH:16]([CH2:26][O:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:15]1)(=O)C.Cl[Sn](Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>C(#N)C>[C:28]([O:27][CH2:26][C@@H:16]1[C:17]([O:22][C:23](=[O:25])[CH3:24])([CH3:21])[C@:18]([F:20])([CH3:19])[CH:14]([N:1]2[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]2=[O:3])[O:15]1)(=[O:35])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 1135ThymineHCID 24287Tin tetrachlorideHCID 516892Sodium BicarbonateHCID 86634318HCID 86634318, compound

Product 1

HCID 57867391HCID 57867391, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of thymine (about 0.68 g, 5.43 mmol) in acetonitrile (about 15 ml) was added compound N,O-Bis-trimethylsilylacetamide (7.90 ml, 32.6 mmol) at room temperature and refluxed for about 2 hours. To this added (2R,4R)-5-(benzoyloxymethyl)-3-fluoro-3,4-dimethyltetrahydrofuran-2,4-diyl diacetate (about 1.00 g, 2.71 mmol) in acetonitrile (about 15 ml) drop wise at about 0° C. and SnCl4 (about 0.47 ml, 4.00 mmol) then refluxed for about 15 hours. Completion of the reaction monitored by thin-layer chromatography, neutralized the reaction mixture with saturated sodium bicarbonate, aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over sodium sulphate. Concentrated under reduced pressure and purified by silica gel column chromatography using 3% methanol in dichloromethane as eluent furnished title compound (0.40 g) as a colorless solid. Yield: 34%; 1H NMR (300 MHz, CDCl3): δ 8.07 (s, 1H), 8.05-8.04 (m, 2H), 7.60-7.58 (m, 1H), 7.49-7.44 (m, 2H), 7.15-7.13 (m, 1H), 6.38 (d, 1H, J=23.1 Hz), 4.74-4.65 (m, 2H), 4.49-4.41 (m, 1H), 2.12 (s, 3H), 1.94 (d, 3H, J=0.9 Hz), 1.83 (d, 3H, J=2.4 Hz), 1.48 (d, 3H, J=23.4 Hz); ES Mass: [M+1] 435 (30%), [M+Na] 457 (100%); IR cm−: 3432, 2926, 1753, 1692, 1602, 1547, 1384, 1276, 1115, 954, 833; HPLC:. 92%.

Workup

  1. temperaturerefluxed for about 2 hours
  2. extractionwas extracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. concentrationConcentrated under reduced pressure
  6. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-9006a84c168447678437b65ade23458c
Source dataset
uspto-grants-2012_07
Patent number
US08227431B2

Reaction notes

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