Ethylamine → 3-Chloro-5-({6-chloro-3-[(ethylamino)methyl]-2-fluorophenyl}oxy)benzonitrile

HRID 1875090Notes

Reaction equation

HRID 1875090 reaction equation
Br[CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[CH2:21]([NH2:23])[CH3:22].C(OCC)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:19][C:17]1[CH:16]=[C:13]([CH:12]=[C:11]([O:10][C:5]2[C:6]([Cl:9])=[CH:7][CH:8]=[C:3]([CH2:2][NH:23][CH2:21][CH3:22])[C:4]=2[F:20])[CH:18]=1)[C:14]#[N:15]

Participants

6

Reactant 4

HCID 6341EthylamineHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 594515763-{[3-(Bromomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 684856043-Chloro-5-({6-chloro-3-[(ethylamino)methyl]-2-fluorophenyl}oxy)benzonitrileYield 106.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-{[3-(bromomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.50 g, 1.33 mmol) in THF (10 mL) was added dropwise to a 2M solution of EtNH2 (6.67 mL, 13.33 mmol) in THF. The flask was sealed and stirred at RT overnight. Ethyl acetate (100 ml) and saturated NaHCO3 solution (100 ml) were added. The organic layer was washed with brine (150 mL), dried over MgSO4, filtered and concentrated to give the title compound (0.48 g, quant.) as a tan solid. 1H NMR shows title compound plus a little residual EtNH2. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.04 (br. s., 1H), 7.83 (s, 1H), 7.62 (s, 2H), 7.45-7.55 (m, 2H), 4.14 (s, 2H), 2.95 (q, 2H), 1.18 (t, 3H). LCMS m/z 340.0 (M+H).

Workup

  1. customThe flask was sealed
  2. washThe organic layer was washed with brine (150 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-bdb3b0006573477385f24c41f39e2d6c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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