Trifluoromethanesulfonic acid → (R)-9-[4-hydroxy-2-(stearoyloxymethyl)butyl]guanine

HRID 1815688Notes

Reaction equation

HRID 1815688 reaction equation
C([O:3][CH:4](OCC)[CH2:5][C@@H:6]([CH2:19][O:20][C:21](=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH2:7][N:8]1[CH:16]=[N:15][C:14]2[C:13](=[O:17])[NH:12][C:11]([NH2:18])=[N:10][C:9]1=2)C.FC(F)(F)S(O)(=O)=O>C1COCC1.O>[OH:3][CH2:4][CH2:5][C@@H:6]([CH2:19][O:20][C:21](=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH2:7][N:8]1[CH:16]=[N:15][C:14]2[C:13](=[O:17])[NH:12][C:11]([NH2:18])=[N:10][C:9]1=2

Participants

5

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 135487833(R)-9-[4,4-diethoxy-2-(stearoyloxymethyl)butyl]guanine

Product 1

HCID 135481053(R)-9-[4-hydroxy-2-(stearoyloxymethyl)butyl]guanine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

The product of Example 30, step d) (3.0 kg) was slurried in THF (46 L) at 20° C. A solution of trifluoromethanesulfonic acid (2.25 kg) in 2.25 kg of water (prepared by slowly adding the acid to cold water) was added and the reaction mixture was stirred at 22° C. for 2 hours. The reaction mixture was cooled to 15° C. and quenched with a solution of NaHCO3 (1.5 kg) in water (5.3 kg). Borane t-butylamine complex (powder, 340 g) was added in four portions and then the reaction temperature was increased to 35° C. and stirred for 12 hours. The reaction mixture was added to a solution of 320 g of concentrated HCl (37% aq.) in 115 kg of tap water at 5° C. This mixture was stirred for 30 minutes and the resulting precipitate was filtered and washed with acetonitrile (15 kg). The solids were reprecipitated once or twice from acetone (35 kg). A final precipitation was accomplished by dissolving the product in THF (24 kg) at 65° C., adding water (1.3 kg), cooling to 30° C. and then adding methylene chloride (105 kg). The resulting slurry was cooled to 10° C. and the precipitate was filtered to provide the desired product.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled to 15° C.
  3. customquenched with a solution of NaHCO3 (1.5 kg) in water (5.3 kg)
  4. additionBorane t-butylamine complex (powder, 340 g) was added in four portions
  5. temperaturethe reaction temperature was increased to 35° C.
  6. stirringstirred for 12 hours
  7. additionThe reaction mixture was added to a solution of 320 g of concentrated HCl (37% aq.) in 115 kg of tap water at 5° C
  8. stirringThis mixture was stirred for 30 minutes
  9. filtrationthe resulting precipitate was filtered
  10. washwashed with acetonitrile (15 kg)
  11. customThe solids were reprecipitated once or twice from acetone (35 kg)
  12. customA final precipitation
  13. dissolutionby dissolving the product in THF (24 kg) at 65° C.
  14. additionadding water (1.3 kg)
  15. temperaturecooling to 30° C.
  16. temperatureThe resulting slurry was cooled to 10° C.
  17. filtrationthe precipitate was filtered

Sources & evidence

ORD record
ord-28ada1b55edf4a4fa0c991c3f30e2458
Source dataset
uspto-grants-2005_04
Patent number
US06878844B2

Reaction notes

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