1,3-Benzodioxole-5-carboxylic acid → HCID 53839260, compound

HRID 1089414Notes

Reaction equation

HRID 1089414 reaction equation
[C:1]([OH:12])(=O)[C:2]1[CH:10]=[CH:9][C:8]2[O:7][CH2:6][O:5][C:4]=2[CH:3]=1.C(N(CC)CC)C.P(Cl)(OCC)(OCC)=O.[Si]([O:36][C@@H:37]1[C@H:41]([O:42][Si](C(C)(C)C)(C)C)[C@@H:40]([CH3:50])[O:39][C@H:38]1[N:51]1[CH:58]=[C:57]([F:59])[C:55]([NH2:56])=[N:54][C:52]1=[O:53])(C(C)(C)C)(C)C>C(#N)C.CN(C)C1C=CN=CC=1>[F:59][C:57]1[C:55]([NH:56][C:1](=[O:12])[C:2]2[CH:10]=[CH:9][C:8]3[O:7][CH2:6][O:5][C:4]=3[CH:3]=2)=[N:54][C:52](=[O:53])[N:51]([CH:58]=1)[C@@H:38]1[O:39][C@H:40]([CH3:50])[C@@H:41]([OH:42])[C@H:37]1[OH:36]

Participants

7

Reactant 4

HCID 71961,3-Benzodioxole-5-carboxylic acidHCID 8471Triethylamine2×HCID 13139Diethyl chlorophosphateHCID 18641814HCID 18641814, compound

Product 1

HCID 53839260HCID 53839260, compoundYield 60.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of piperonylic acid (0.42 g) in dry acetonitrile (5 ml) containing triethylamine (0.36 ml) was treated with diethyl chlorophosphate (0.37 ml) for 1 hour. To the reaction mixture were added 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-fluorocytidine (1.0 g) obtained in Reference example (a), triethylamine (0.36 ml) and 4-dimethylaminopyridine (0.05 g). After stirring of the mixture for 12 hours at room temperature, acetonitrile was evaporated under reduced pressure. The residue was partitioned between water and ether. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained powder was dissolved in tetrahydrofuran (6.3 ml) containing tetrabutylammonium fluoride (1.65 g) and the reaction mixture was stirred for 1 hour. After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (isopropanol-dichloromethane) followed by recrystallization from ethyl acetate to give 0.5 g of 5'-deoxy-5-fluoro-N4 -piperonyloylcytidine, mp 124°~125° C.: MS 394 (MH+).

Workup

  1. customacetonitrile was evaporated under reduced pressure
  2. customThe residue was partitioned between water and ether
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe obtained powder was dissolved in tetrahydrofuran (6.3 ml)
  7. additioncontaining tetrabutylammonium fluoride (1.65 g)
  8. stirringthe reaction mixture was stirred for 1 hour
  9. customAfter removal of the solvent under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (isopropanol-dichloromethane)
  11. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-5227b8eb3cbf4fbfb9634cac7dcf3d03
Source dataset
uspto-grants-1990_10
Patent number
US04966891

Reaction notes

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