Ammonium Hydroxide → N2-[4-Cyano-3-(trifluoromethyl)phenyl]-N2-(2,2-dimethylpropyl)glycinamide

HRID 2109106Notes

Reaction equation

HRID 2109106 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][C:11]([OH:13])=O)=[CH:5][C:4]=1[C:19]([F:22])([F:21])[F:20])#[N:2].C(Cl)(=O)C(Cl)=O.[NH4+:29].[OH-]>C(Cl)Cl.CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:14][C:15]([CH3:16])([CH3:18])[CH3:17])[CH2:10][C:11]([NH2:29])=[O:13])=[CH:5][C:4]=1[C:19]([F:22])([F:20])[F:21])#[N:2]

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 65578Oxalyl chlorideHCID 11278444N-[4-Cyano-3-(trifluoromethyl)phenyl]-N-(2,2-dimethylpropyl)glycine

Product 1

HCID 11232234N2-[4-Cyano-3-(trifluoromethyl)phenyl]-N2-(2,2-dimethylpropyl)glycinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2-dimethylpropyl)glycine (1.13 g, 3.58 mmol) in CH2Cl2 (10 mL) at 0° C. was added oxalyl chloride (0.33 mL, 3.76 mmol), followed by DMF (0.01 mL, 0.2 mmol). The resulting solution was stirred 5 min in the cooling bath, 20 min at rt and 1 h at reflux under N2. After cooling to rt, the solution was slowly poured into NH4OH (10 mL of a 30 wt % solution) at 0° C., stirred 30 min, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4, filtered and concentrated in vacuo. The crude product was recrystallized from IPA/hexanes, affording 0.642 g of the title compound as a colorless, amorphous solid. The mother liquor was concentrated and purified by flash chromatography (EtOAc/hexanes), affording an additional 0.241 g of the title compound: 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=8.9 Hz, 1H), 7.07 (d, J=2.5 Hz, 1H), 6.85 (dd, J=8.9, 2.6 Hz, 1H), 5.70 (bs, 1H), 5.59 (bs, 1H), 4.12 (s, 2H), 3.38 (s, 2H), 1.03 (s, 9H).

Workup

  1. temperatureat reflux under N2
  2. temperatureAfter cooling to rt
  3. stirringstirred 30 min
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with CH2Cl2 (×2)
  6. washcombined organics were washed (water, brine)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was recrystallized from IPA/hexanes

Sources & evidence

ORD record
ord-11c8ee57205f482dbf49ba36ac9d4b7f
Source dataset
uspto-grants-2009_04
Patent number
US07514470B2

Reaction notes

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