Oxalyl chloride → N-[4-cyano-3-(trifluoromethyl)phenyl]-2,2,4-trimethyl-1,3-dioxolane-4-carboxamide

HRID 2415420Notes

Reaction equation

HRID 2415420 reaction equation
C(Cl)(=O)C(Cl)=O.[Na].[CH3:8][C:9]1([CH3:18])[O:13][C:12]([CH3:17])([C:14]([O-:16])=O)[CH2:11][O:10]1.[Na+].[C:20]([C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][C:23]=1[C:29]([F:32])([F:31])[F:30])#[N:21].C([O-])(O)=O.[Na+]>O1CCCC1.C(N(CC)CC)C.CC(N(C)C)=O.C(OCC)(=O)C.CCCCCCC>[C:20]([C:22]1[CH:28]=[CH:27][C:25]([NH:26][C:14]([C:12]2([CH3:17])[CH2:11][O:10][C:9]([CH3:8])([CH3:18])[O:13]2)=[O:16])=[CH:24][C:23]=1[C:29]([F:30])([F:31])[F:32])#[N:21]

Participants

10

Reactant 5

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 5221704-Amino-2-(trifluoromethyl)benzonitrileHCID 5360545SodiumHCID 23525849Sodium 2,2,4-trimethyl-1,3-dioxolane-4-carboxylate

Product 1

HCID 22641284N-[4-cyano-3-(trifluoromethyl)phenyl]-2,2,4-trimethyl-1,3-dioxolane-4-carboxamideYield 51%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 31374DimethylacetamideSolvent2×HCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
-10 °C

Procedure

In a 50 ml 3-necked flask, equipped with a magnetic stirrer, under nitrogen at −20° C., 0.3 ml of oxalyl chloride in 1 ml of tetrahydrofuran was added slowly to 0.364 g of the sodium salt of the Example 5 (compound (8), R═Na) in a mixture of 0.5 ml of triethyl amine in 5 ml of dimethylacetamide. The resulting mixture was stirred for 30 minutes at −10° C. Then, a solution of 0.372 g of 4-cyano-3-trifluoromethylaniline in 2 ml of dimethylacetamide was added dropwise and slowly. The conversion was followed by TLC analysis (eluens: ethyl acetate/heptane=2/3). After ˜1 hour at room temperature, the reaction mixture was poured into 200 ml of saturated aqueous NaHCO3 solution, and was subsequently extracted with 2×30 ml of ethyl acetate. The combined organic layers were washed with 50 ml of brine, dried (Na2SO4) and concentrated at reduced pressure to give a dark-brown oil, which was purified by column chromatography (Merck 60 SiO2, eluens ethyl acetate/heptane=2/3). Isolated yield: 0.336 g light brown clear oil (51%). 1H-NMR confirmed the structure.

Workup

  1. customIn a 50 ml 3-necked flask, equipped with a magnetic stirrer, under nitrogen at −20° C.
  2. waitAfter ˜1 hour at room temperature
  3. extractionwas subsequently extracted with 2×30 ml of ethyl acetate
  4. washThe combined organic layers were washed with 50 ml of brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated at reduced pressure
  7. customto give a dark-brown oil, which
  8. customwas purified by column chromatography (Merck 60 SiO2, eluens ethyl acetate/heptane=2/3)

Sources & evidence

ORD record
ord-56aafc6948c648b48a69eaca8e1dd6d0
Source dataset
uspto-grants-2004_11
Patent number
US06818766B2

Reaction notes

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