Sodium Bicarbonate → Ethyl 3-[(2-chloro-5-nitropyrimidin-4-YL)(cyclopentyl)amino]-2,2-difluoropropanoate

HRID 2111434Notes

Reaction equation

HRID 2111434 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]([F:14])([F:13])[CH2:6][NH:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)[CH3:2].[Cl:16][C:17]1[N:22]=[C:21](Cl)[C:20]([N+:24]([O-:26])=[O:25])=[CH:19][N:18]=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]([F:14])([F:13])[CH2:6][N:7]([C:19]1[C:20]([N+:24]([O-:26])=[O:25])=[CH:21][N:22]=[C:17]([Cl:16])[N:18]=1)[CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)[CH3:2]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 57634998Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate

Product 1

HCID 57955636Ethyl 3-[(2-chloro-5-nitropyrimidin-4-YL)(cyclopentyl)amino]-2,2-difluoropropanoateYield 103.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 3.6 g (0.016 mole) of 3-cyclopentylamino-2,2-difluoro-propanoic acid ethyl ester in 3 mL of ethyl acetate was added over 5 minutes to a cooled (0 degrees) mixture of 3.2 g (0.016 mole) of 2,4-dichloro-5-nitro-pyrimidine, 5.47 g (0.064 mole) of sodium bicarbonate and 36 mL of ethyl acetate. The cooling bath was removed and the mixture stirred for 17 hours at room temperature. Activated charcoal was added and after stirring briefly, the mixture was filtered through a pad of Celite, washing the filter pad with ethyl acetate. The filtrate was concentrated under reduced pressure to give 6.29 g of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-2,2-difluoro-propanoic acid ethyl ester (IV-100) as a yellow thick oil, which contained a small portion of a regioisomer. This material was used directly in the next step without further purification.

Workup

  1. temperaturea cooled
  2. customThe cooling bath was removed
  3. additionActivated charcoal was added
  4. stirringafter stirring briefly
  5. filtrationthe mixture was filtered through a pad of Celite
  6. washwashing the filter pad with ethyl acetate
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-0328a426a1b948c08dec1a8f5d87936c
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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