Sodium Hydroxide → (+)-5-Methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro-2-oxo-6 (s)-(3,4-difluorophenyl)-1-[(2-carboxyethylamino)-carbonyl]pyrimidine

HRID 1840325Notes

Reaction equation

HRID 1840325 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C@H:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[N:9]([C:19]([NH:21][CH2:22][CH2:23][C:24]([O:26]CC)=[O:25])=[O:20])[C:8](=[O:29])[NH:7][C:6]=1[CH2:30][O:31][CH3:32])=[O:4].[OH-].[Na+]>CO>[CH3:1][O:2][C:3]([C:5]1[C@H:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[N:9]([C:19]([NH:21][CH2:22][CH2:23][C:24]([OH:26])=[O:25])=[O:20])[C:8](=[O:29])[NH:7][C:6]=1[CH2:30][O:31][CH3:32])=[O:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 60101878(+)-5-Methoxycarbonyl-4-methyoxymethyl-1, 2,3,6-tetrahydro-2-oxo-6(S)-(3,4-difluorophenyl)-1-[(2-ethoxycarbonylethylamino)carbonyl]pyrimidine

Product 1

HCID 59965090(+)-5-Methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro-2-oxo-6 (s)-(3,4-difluorophenyl)-1-[(2-carboxyethylamino)-carbonyl]pyrimidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(+)-5-Methoxycarbonyl-4-methyoxymethyl-1,2,3,6-tetrahydro-2-oxo-6(S)-(3,4-difluorophenyl)-1-[(2-ethoxycarbonylethylamino)carbonyl]pyrimidine (168 mg, 0.37 mmol) was dissolved in 5 mL of methanol. A 2.0M solution of aqueous sodium hydroxide (400 mL, 0.80 mmol) was added dropwise. The mixture was stirred at ambient temperature for 4.5 hours, then concentrated in vacuo. The resulting residue was partioned between ethyl acetate and 2.0M aqueous hydrochloric acid. The phases were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were then washed with brine. The organic phase was then dried over sodium sulfate, filtered, and the filtrate was then evaporated to dryness. The residue was reconcentrated from diethyl ether. The resulting white foamy solid was purified by “flash” chromatography (5.02, 98:2:0.2 of dichloromethane:methanol:glacial acetic acid). The product fractions were evaporated to dryness and the residue was reconcentrated from diethyl ether to give the title compound as a white foamy solid.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted twice with ethyl acetate
  4. washThe combined organic phases were then washed with brine
  5. dry with materialThe organic phase was then dried over sodium sulfate
  6. filtrationfiltered
  7. customthe filtrate was then evaporated to dryness
  8. customThe resulting white foamy solid was purified by “flash” chromatography (5.02, 98:2:0.2 of dichloromethane:methanol:glacial acetic acid)
  9. customThe product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-305dae6b63d54bc39d81418cd66cc7fc
Source dataset
uspto-grants-2004_01
Patent number
US06680323B2

Reaction notes

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