Formic Acid → HCID 69758553, compound

HRID 392324Notes

Reaction equation

HRID 392324 reaction equation
[P:1]([O:27]CC=C)([O:23]CC=C)([O:3][CH2:4][C@@H:5]1[C@@H:9]([OH:10])[C@@H:8]([OH:11])[C@H:7]([N:12]2[CH:17]=[C:16]([F:18])[N:15]=[C:14]([C:19]([NH2:21])=[O:20])[C:13]2=[O:22])[O:6]1)=[O:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)=O.C(N)CCC>CO.O1CCCC1.O>[CH2:7]([NH2:12])[CH2:8][CH2:9][CH3:5].[P:1]([OH:27])([OH:23])([O:3][CH2:4][C@@H:5]1[C@@H:9]([OH:10])[C@@H:8]([OH:11])[C@H:7]([N:12]2[CH:17]=[C:16]([F:18])[N:15]=[C:14]([C:19]([NH2:21])=[O:20])[C:13]2=[O:22])[O:6]1)=[O:2]

Participants

8

Reactant 4

HCID 284Formic AcidHCID 8007ButylamineHCID 11776TriphenylphosphineHCID 60126645HCID 60126645, compound

Product 1

HCID 69758553HCID 69758553, compoundYield 71.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

In a mixture of 8.2 mL of methanol and 8.2 mL of tetrahydrofuran was dissolved 0.82 g of {(2R,3S,4R,5R)-5-[3-(aminocarbonyl)-5-fluoro-2-oxo-1(2H)-pyrazinyl]-3,4-dihydroxytetrahydro-2-furanyl}methyl diallyl phosphate under a stream of nitrogen gas. After adding 0.11 g of tetrakis-triphenylphosphine palladium (0) and 0.28 g of triphenylphosphine successively, the mixture thus obtained was stirred at room temperature for 30 minutes. While cooling the reaction mixture with ice, a solution of 0.68 mL of formic acid in 1.9 mL of tetrahydrofuran and a solution of 0.25 mL of n-butylamine in 8.2 mL of tetrahydrofuran were successively added. The mixture thus obtained was stirred at 30-35° C. for one hour and then at 40-45° C. for 2 hours. The reaction mixture was diluted with 10 mL of water, and the organic solvent was removed under reduced pressure. The aqueous solution thus obtained was washed with 20 mL of chloroform, and the washings were extracted with 30 mL of water. All the aqueous layers were united, and the solvent was removed under reduced pressure. The residue thus obtained was purified by reversed phase silica gel column chromatography [eluent: water]. Thus, 0.29 g of {(2R,3S,4R,5R)-5-[3-(aminocarbonyl)-5-fluoro-2-oxo-1(2H)-pyrazinyl]-3,4-dihydroxytetrahydro-2-furanyl}methyl dihydrogen phosphate n-butylamine salt was obtained as a yellow-colored solid product.

Workup

  1. customthe mixture thus obtained
  2. temperatureWhile cooling the reaction mixture with ice
  3. customThe mixture thus obtained
  4. stirringwas stirred at 30-35° C. for one hour
  5. waitat 40-45° C. for 2 hours
  6. customthe organic solvent was removed under reduced pressure
  7. customThe aqueous solution thus obtained
  8. washwas washed with 20 mL of chloroform
  9. extractionthe washings were extracted with 30 mL of water
  10. customthe solvent was removed under reduced pressure
  11. customThe residue thus obtained
  12. customwas purified by reversed phase silica gel column chromatography [eluent: water]

Sources & evidence

ORD record
ord-965af041c0434ee58a10a75218ea329e
Source dataset
uspto-grants-2004_10
Patent number
US06800629B2

Reaction notes

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