Bromoacetonitrile → 2-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetonitrile

HRID 1845929Notes

Reaction equation

HRID 1845929 reaction equation
[H-].[Na+].[F:3][C:4]([F:23])([F:22])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16](=[O:21])[CH2:15][CH2:14]3)=[CH:7][CH:6]=1.Br[CH2:25][C:26]#[N:27]>CN(C)C=O>[O:21]=[C:16]1[CH2:15][CH2:14][C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:8]3[CH:7]=[CH:6][C:5]([C:4]([F:3])([F:22])[F:23])=[CH:10][CH:9]=3)[CH:12]=2)[N:17]1[CH2:25][C:26]#[N:27]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 120009366-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 462023902-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 95% dry sodium hydride (48 mg, 2.00 mmol) in anhydrous N,N-dimethylformamide (10 mL) at room temperature was added a solution of 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one (291 mg, 1.00 mmol). The reaction mixture was stirred for 30 minutes under an atmosphere of dry N2, followed by addition of a solution of 2-bromoacetonitrile (480 mg, 4.00 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was stirred at room temperature until the majority of the starting material was converted (as checked by LCMS), then quenched by addition of methanol (10 mL). The mixture was concentrated under reduced pressure, and the residue was subjected to reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford 2-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetonitrile (compound No. 90) (307 mg, 0.93 mmol, 93%). LCMS mz 331.0 (M+H), 353.0 (M+Na), anal HPLC >98% in purity. 1H NMR (400 MHz; CDCl3) δ 7.69 (m, 4H); 7.57 (dd, J=8.4 and 2.1 Hz, 1H); 7.47 (d, J=3.0 Hz, 1H); 7.16 (d, J=8.2 Hz, 1H); 6.90 (s, 2H); 3.05 (m, 2H); 2.79 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature until the majority of the starting material
  2. customquenched by addition of methanol (10 mL)
  3. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-5007d78f576449abae9d48d7e7a775f8
Source dataset
uspto-grants-2015_02
Patent number
US08952007B2

Reaction notes

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