Diethyl Ether → 2,6-Difluoro-N,N-di(propan-2-yl)benzene-1-carboximidamide

HRID 2421446Notes

Reaction equation

HRID 2421446 reaction equation
CC[Mg+].[Br-].CCOCC.[CH:10]([NH:13][CH:14]([CH3:16])[CH3:15])([CH3:12])[CH3:11].[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:19]=1[C:20]#[N:21]>C1(C)C=CC=CC=1>[CH:10]([N:13]([CH:14]([CH3:16])[CH3:15])[C:20](=[NH:21])[C:19]1[C:18]([F:17])=[CH:25][CH:24]=[CH:23][C:22]=1[F:26])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 7912DiisopropylamineHCID 746952,6-DifluorobenzonitrileHCID 178461630HCID 178461630, compound

Product 1

HCID 237265252,6-Difluoro-N,N-di(propan-2-yl)benzene-1-carboximidamideYield 93.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of EtMgBr in ether (8.0 mL, 3.0 M, 24 mmol) was added to a solution of diisopropylamine (2.50 g, 24.8 mmol) in toluene (60 mL) at 50° C. The mixture was stirred for 1 h and a white precipitate formed. Next, the mixture was cooled to 0° C. and 2,6-difluorobenzonitrile (3.34 g, 24 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 16 h subsequently. The conversion, determined by GC, appeared to be 98%. The mixture was quenched with an aqueous NH4Cl solution (1%, 100 mL). The organic phase was separated from the aqueous phase and the latter was extracted with diethylether (200 mL) twice. The combined organic phases were dried over Na2SO4, filtered and the solvents were removed under reduced pressure giving 5.40 g (91%) of pure product. The ligand was characterized by 1H NMR (300 MHz) (CDCl3) δ (ppm): 7.2 (m, 1H), 6.8 (m, 2H), 5.5 (bs, 1H), 3.7 (bs, 1H), 3.4 (bs, 1H), 1.5 (bs, 6H), 1.0 (bs, 6H), by 13C NMR 75 MHz (CDCl3) δ (ppm): 158.9 (dd, J=248 Hz, J=8 Hz), 155.7, 130.1, 130.0, 129.8, 112.1, 112.0, 111.9, 111.852.0 (bs), 46.2 (bs), 21.3, 20.5 and by 19F (282 MHz) (CDCl3) δ (ppm) −114.

Workup

  1. customa white precipitate formed
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 h subsequently
  4. customThe mixture was quenched with an aqueous NH4Cl solution (1%, 100 mL)
  5. customThe organic phase was separated from the aqueous phase
  6. extractionthe latter was extracted with diethylether (200 mL) twice
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-4b8a9fc0b2a549819f7ae12f52bab4ab
Source dataset
uspto-grants-2011_06
Patent number
US07956140B2

Reaction notes

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