Ammonium fluoride → Sonedenoson

HRID 1392005Notes

Reaction equation

HRID 1392005 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:21]1[O:35][C@H:34]([C:36](C)(C)[O:37]C(C)(C)C)[C@@H:28]([O:29]C(C)(C)C)[C@H:22]1[O:23]C(C)(C)C.[F-].[NH4+]>CO>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][CH2:12][O:11][C:9]2[N:10]=[C:2]([NH2:1])[C:3]3[N:4]=[CH:5][N:6]([C:7]=3[N:8]=2)[C@@H:21]2[O:35][C@H:34]([CH2:36][OH:37])[C@@H:28]([OH:29])[C@H:22]2[OH:23])=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 25516Ammonium fluorideHCID 1317268006-amino-2-[2-(4-chlorophenyl)ethoxy]-9-(2,3,5-tri-O-tert-butyldimethyl-beta-D-ribofuranosyl)purine

Product 1

HCID 9910098SonedenosonYield 59.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3438.4 g (4.51 mol) of 6-amino-2-[2-(4-chlorophenyl)ethoxy]-9-(2,3,5-tri-O-tert-butyldimethyl-β-D-ribofuranosyl)purine in 48.4 L of methanol was added 1.679 g (45.32 mol) of ammonium fluoride. The solution was heated to reflux and monitored by HPLC to determine completion. The reaction was allowed to cool to room temperature and the solvent was concentrated under reduced pressure. The reaction mixture was partitioned between water (17.3 L) and ethyl acetate (17.3 L). The aqueous layer was washed again with ethyl acetate (17.4 L). The combined organic layers were dried over magnesium sulfate (1000 g), filtered and removed under reduced pressure. The resultant solid was recrystallized from ethanol (9.87 L) to yield an off-white solid (1139 g, 59.8% yield).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux
  3. concentrationthe solvent was concentrated under reduced pressure
  4. customThe reaction mixture was partitioned between water (17.3 L) and ethyl acetate (17.3 L)
  5. washThe aqueous layer was washed again with ethyl acetate (17.4 L)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate (1000 g)
  7. filtrationfiltered
  8. customremoved under reduced pressure
  9. customThe resultant solid was recrystallized from ethanol (9.87 L)

Sources & evidence

ORD record
ord-a24ccedc7beb4d729a02c600fa3809c3
Source dataset
uspto-grants-2008_03
Patent number
US07342003B2

Reaction notes

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