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

HRID 1676825Notes

Reaction equation

HRID 1676825 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[C:5]([F:18])([F:17])[CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[CH3:2].[Cl:20][C:21]1[N:26]=[C:25](Cl)[C:24]([N+:28]([O-:30])=[O:29])=[CH:23][N:22]=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:19])[C:5]([F:18])([F:17])[CH2:6][N:7]([C:23]1[C:24]([N+:28]([O-:30])=[O:29])=[CH:25][N:26]=[C:21]([Cl:20])[N:22]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[CH3:2]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 5212662,4-Dichloro-5-nitropyrimidineHCID 580149953-(4-Methoxybenzylamino)-2,2-difluoropropionic acid ethyl ester

Product 1

HCID 866375213-[(2-Chloro-5-nitro-pyrimidin-4-yl)-(4-methoxy-benzyl)-amino]-2,2-difluoro-propionic acid ethyl esterYield 100.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 1.2 g (0.0044 mole) of 2,2-difluoro-3-(4-methoxy-benzylamino)-propionic acid ethyl ester) in 4 mL of ethyl acetate was added over 5 minutes to a cooled (0 degrees) mixture of 0.85 g (0.0044 mole) of 2,4-dichloro-5-nitro-pyrimidine, 1.5 g (0.018 mole) of sodium bicarbonate and 10 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 1.9 g of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-(4-methoxy-benzyl)-amino]-2,2-difluoro-propionic acid ethyl ester (IV-291) as a yellow thick oil. 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-cc03866605484ff0a3ca5f75d53b55df
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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