Sodium Bicarbonate → 3-[(2-Chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2,2-difluoro-propionic acid ethyl ester

HRID 1676536Notes

Reaction equation

HRID 1676536 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[C:5]([F:13])([F:12])[CH2:6][NH:7][CH:8]1[CH2:11][CH2:10][CH2:9]1)[CH3:2].[Cl:15][C:16]1[N:21]=[C:20](Cl)[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:14])[C:5]([F:13])([F:12])[CH2:6][N:7]([C:18]1[C:19]([N+:23]([O-:25])=[O:24])=[CH:20][N:21]=[C:16]([Cl:15])[N:17]=1)[CH:8]1[CH2:11][CH2:10][CH2:9]1)[CH3:2]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 580151203-Cyclobutylamino-2,2-difluoropropionic acid ethyl ester

Product 1

HCID 866375013-[(2-Chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2,2-difluoro-propionic acid ethyl esterYield 37%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 17.76 g (0.086 mole) 3-cyclobutylamino-2,2-difluoropropionic acid ethyl ester in 10 mL of ethyl acetate was added dropwise to a mixture of 16.6 g (0.086 mole) of 2,4-dichloro-5-nitro-pyrimidine, 28.9 g (0.344 mole) of sodium bicarbonate and 100 mL of ethyl acetate at 0 degrees. The cooling bath was removed and the reaction was stirred at room temperature for 18 h. Activated charcoal was added, and the mixture was filtered through a pad of Celite, washing the filter pad with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue purified by silica gel chromatography (elution with hexanes-ethyl acetate, gradient 100:0-50:50), to give 11.6 g of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2,2-difluoro-prop ionic acid ethyl ester (IV-1).

Workup

  1. customThe cooling bath was removed
  2. additionActivated charcoal was added
  3. filtrationthe mixture was filtered through a pad of Celite
  4. washwashing the filter pad with ethyl acetate
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue purified by silica gel chromatography (elution with hexanes-ethyl acetate, gradient 100:0-50:50)

Sources & evidence

ORD record
ord-192f8ba4b4684455a09f733b46bcf42b
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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