Cesium carbonate → Methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinate

HRID 1173403Notes

Reaction equation

HRID 1173403 reaction equation
[F:1][C:2]([F:18])([F:17])[CH2:3][NH:4][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.Br[CH2:20][C:21]([O:23][CH3:24])=[O:22].C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C>[C:9]([C:8]1[CH:11]=[CH:12][C:5]([N:4]([CH2:3][C:2]([F:17])([F:18])[F:1])[CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:6][C:7]=1[C:13]([F:16])([F:14])[F:15])#[N:10]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 431385374-((2,2,2-Trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile

Product 1

HCID 11439223Methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinateYield 74.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(2,2,2-trifluoro-ethylamino)-2-trifluoromethyl-benzonitrile (5.00 g, 18.7 mmol), methyl bromoacetate (3.25 mL, 37.5 mmol), and Cs2CO3 (12.2 g, 37.3 mmol) in acetonitrile (50 mL) was held at reflux, under N2, for 2 h and cooled to rt, and solids were removed by filtration. The filtrate was adsorbed onto a minimal amount of silica gel, filtered through a short pad of silica gel (EtOAc/hexanes) and concentrated to dryness. Recrystallization from EtOAc/hexanes afforded 4.72 g of the title compound as fine needles, mp 144-145° C.: 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J=8.9 Hz, 1H), 7.01 (d, J=2.3 Hz, 1H), 6.88 (dd, J=2.6 Hz, 1H), 4.24 (s, 2H), 4.06 (q, J=8.5 Hz, 2H), 3.81 (s, 3H).

Workup

  1. temperatureat reflux, under N2, for 2 h
  2. customsolids were removed by filtration
  3. filtrationfiltered through a short pad of silica gel (EtOAc/hexanes)
  4. concentrationconcentrated to dryness
  5. customRecrystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-f4d776da7279437c9c42c373dd704cd5
Source dataset
uspto-grants-2010_11
Patent number
US07834063B2

Reaction notes

Loading…