2-Methyl-2-butene → N-[4-Cyano-3-(trifluoromethyl)phenyl]-N-(2,2-dimethylpropyl)glycine

HRID 2109105Notes

Reaction equation

HRID 2109105 reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[CH2:3][N:4]([CH2:17][CH:18]=[O:19])[C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([C:13]([F:16])([F:15])[F:14])[CH:6]=1.CC(=CC)C.[O-:27]Cl=O.[Na+].[OH-].[Na+]>CC(O)(C)C.O>[C:9]([C:8]1[CH:11]=[CH:12][C:5]([N:4]([CH2:3][C:2]([CH3:21])([CH3:20])[CH3:1])[CH2:17][C:18]([OH:27])=[O:19])=[CH:6][C:7]=1[C:13]([F:14])([F:15])[F:16])#[N:10]

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 14798Sodium HydroxideHCID 11289510HCID 11289510, compoundHCID 23668197Sodium Chlorite

Product 1

HCID 11278444N-[4-Cyano-3-(trifluoromethyl)phenyl]-N-(2,2-dimethylpropyl)glycineYield 91.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a stirred slurry of 4-[(2,2-dimethylpropyl)(2-oxoethyl)amino]-2-(trifluoromethyl)benzonitrile (1.20 g, 4.03 mmol) and 2-methyl-2-butene (4.3 mL, 40 mmol) in t-BuOH (30 mL) at rt was added a solution of NaClO2 (0.591 g of 80% tech. grade; 5.2 mmol) in NaH2PO4 buffer (6 mL, 1.5 M NaH2PO4, adjusted to pH 3.5 with 1 N HCl), dropwise over 5 min (slightly exothermic). After complete dissolution of slurried solids, the flask was stoppered with a rubber septum and placed under balloon pressure of nitrogen for 3 h. Water (100 mL) was added, the whole was adjusted to ca. pH 11 by addition of 15 wt % NaOH, and partially concentrated in vacuo. The aqueous residue was extracted with Et2O (×2), adjusted to ca. pH 1 by addition of 2 N HCl and extracted with EtOAc (×3). The combined EtOAc extracts were washed (brine), dried over Na2SO4, filtered and concentrated to dryness, affording 1.16 g of the title compound as a colorless foam: 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J=8.9 Hz, 1H), 7.01 (d, J=2.2 Hz, 1H), 6.79 (dd, J=8.9, 2.5 Hz, 1H), 4.24 (s, 2H), 3.31 (s, 2H), 1.02 (s, 9H).

Workup

  1. dissolutionAfter complete dissolution of slurried solids
  2. waitplaced under balloon pressure of nitrogen for 3 h
  3. concentrationpartially concentrated in vacuo
  4. extractionThe aqueous residue was extracted with Et2O (×2)
  5. additionadjusted to ca. pH 1 by addition of 2 N HCl
  6. extractionextracted with EtOAc (×3)
  7. washThe combined EtOAc extracts were washed (brine)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-fe73902d78ee475cbf76048e49fa8f34
Source dataset
uspto-grants-2009_04
Patent number
US07514470B2

Reaction notes

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