Dimethylformamide → HCID 57633767, compound

HRID 2109101Notes

Reaction equation

HRID 2109101 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:16][C:17]([F:20])([F:19])[F:18])[CH2:10][CH:11]([CH3:15])[C:12]([OH:14])=O)=[CH:5][C:4]=1[C:21]([F:24])([F:23])[F:22])#[N:2].C(Cl)(=O)C(Cl)=O.C[N:32](C=O)C.[NH4+].[OH-]>C(Cl)Cl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:16][C:17]([F:20])([F:19])[F:18])[CH2:10][CH:11]([CH3:15])[C:12]([NH2:32])=[O:14])=[CH:5][C:4]=1[C:21]([F:23])([F:24])[F:22])#[N:2]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 14923Ammonium HydroxideHCID 65578Oxalyl chloride2×HCID 57633744HCID 57633744, compound

Product 1

HCID 57633767HCID 57633767, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
42 °C

Procedure

To an ice-cold solution of 3-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]-2-methylpropanoic acid (0.050 g, 0.14 mmol) in CH2Cl2 (3 mL), under nitrogen was added oxalyl chloride (0.023 g, 0.18 mmol) and DMF (cat) and the mixture was heated at 42° C. for 30 min. Upon cooling, additional oxalyl chloride (0.014 g, 0.11 mmol) and DMF (cat.) were added and heated for 30 min. Upon cooling, NH4OH (30% aqueous solution, 5 mL) was added and the mixture stirred at rt. After 1 h, the mixture was partitioned between CH2Cl2 and water. The organic phase was washed with 0.1N HCl and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (1-5% MeOH—CH2Cl2 gradient) to give the title compound (0.044 g, 88% yield): 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J=8.6 Hz, 1H), 7.01 (d, J=2.6 Hz, 1H), 6.89 (dd, J=8.6, 2.6 Hz, 1H), 5.70 (bs, NH), 5.54 (bs, NH), 4.22-4.08 (m, 2H), 3.85 (dd, J=15.4, 10.3 Hz, 1H), 3.54 (dd, J=15.4, 3.7 Hz, 1H), 2.80-2.70 (m, 1H), 1.23 (d, J=7.0 Hz, 3H).

Workup

  1. temperatureUpon cooling
  2. temperatureheated for 30 min
  3. temperatureUpon cooling
  4. customthe mixture was partitioned between CH2Cl2 and water
  5. washThe organic phase was washed with 0.1N HCl and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (1-5% MeOH—CH2Cl2 gradient)

Sources & evidence

ORD record
ord-6a9fb5631c0f4997b767d71d0d0e5c3f
Source dataset
uspto-grants-2009_04
Patent number
US07514470B2

Reaction notes

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