Carbon Dioxide → Emtricitabine

HRID 1359459Notes

Reaction equation

HRID 1359459 reaction equation
Cl.[NH2:2][C:3]1[C:8]([F:9])=[CH:7][N:6]([C@H:10]2[O:14][C@@H:13]([CH2:15][OH:16])[S:12][CH2:11]2)[C:5](=[O:17])[N:4]=1.CO.C([O-])([O-])=O.[Na+].[Na+].C(=O)=O>C(OCC)(=O)C>[CH2:11]1[S:12][C@H:13]([CH2:15][OH:16])[O:14][C@@H:10]1[N:6]1[C:5](=[O:17])[N:4]=[C:3]([NH2:2])[C:8]([F:9])=[CH:7]1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 887MethanolHCID 10340Sodium CarbonateHCID 53311196HCID 53311196, compound

Product 1

HCID 60877Emtricitabine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 250 mL round bottom flask, fitted with a magnetic stirrer, are added cis-(−)-4-amino-5-fluoro-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-2(1H)-pyrimidinone HCl salt (5 g, 17.63 mmol, 99.4% purity) and methanol (25 mL). The mixture is stirred at room temperature, and to it is added Na2CO3 solid (1.12 g, 10.6 mmol). CO2 gas comes out immediately after the addition. Upon being stirred at room temperature for 3 hours, the reaction mixture is diluted with ethyl acetate (125 mL) and stirred at room temperature for 1 hour. Then the mixture is filtered through a silica gel-Celite pad, and the pad is washed with ethyl acetate-methanol (5:1, v/v) (20 mL). The filtrate is concentrated at 40-50° C. to 20 mL, and to it is added ethanol (5 mL). The resulting mixture is stirred at 60° C. for 15 minutes, then cooled to 0° C. and stirred at 0° C. for 1.5 hours. The mixture is filtered and the solid cake is washed with ethyl acetate. The solid is dried in vacuum at 45° C. for 12 hours to afford (−)-FTC as white solids (3.7 g, 86%, HPLC assay: 99.7% purity). The mother liquid is concentrated to 5 mL, and stirred at room temperature. Filtration gave (−)-FTC as white crystals (0.2 g, 4.7%).

Workup

  1. customTo a 250 mL round bottom flask, fitted with a magnetic stirrer
  2. additionafter the addition
  3. stirringUpon being stirred at room temperature for 3 hours
  4. stirringstirred at room temperature for 1 hour
  5. filtrationThen the mixture is filtered through a silica gel-Celite pad
  6. washthe pad is washed with ethyl acetate-methanol (5:1
  7. concentrationThe filtrate is concentrated at 40-50° C. to 20 mL
  8. additionto it is added ethanol (5 mL)
  9. stirringThe resulting mixture is stirred at 60° C. for 15 minutes
  10. temperaturecooled to 0° C.
  11. stirringstirred at 0° C. for 1.5 hours
  12. filtrationThe mixture is filtered
  13. washthe solid cake is washed with ethyl acetate
  14. customThe solid is dried in vacuum at 45° C. for 12 hours

Sources & evidence

ORD record
ord-5b799adc592a4c4a9a31847ea19e8e91
Source dataset
uspto-grants-2003_07
Patent number
US06600044B2

Reaction notes

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