Diethanolamine → 3,5-Difluoro-4-[bis(2-hydroxyethyl)amino]benzonitrile

HRID 23608Notes

Reaction equation

HRID 23608 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1F)[C:5]#[N:6].[NH:12]([CH2:16][CH2:17][OH:18])[CH2:13][CH2:14][OH:15]>CN(C)C(=O)C>[F:11][C:8]1[CH:7]=[C:4]([CH:3]=[C:2]([F:1])[C:9]=1[N:12]([CH2:16][CH2:17][OH:18])[CH2:13][CH2:14][OH:15])[C:5]#[N:6]

Participants

4

Reactant 2

HCID 8113DiethanolamineHCID 5938143,4,5-Trifluorobenzonitrile

Product 1

HCID 225901583,5-Difluoro-4-[bis(2-hydroxyethyl)amino]benzonitrile

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 3,4,5-trifluorobenzonitrile (5 g, 32 mmol) and diethanolamine (6 ml, 85 mmol) in N,N-dimethylacetamide was stirred for 10 days. The solvent was then evaporated, the residue partitioned between CH2Cl2 (200 ml) and H2O (200 ml), the organic layer dried (MgSO4) and evaporated to dryness. The residue was chromatographed using CH2Cl2-EtOAc as eluent to give, after recrystallization from toluene, 2.7 g (35%) of pure white crystals: mp 63-65° C.; 1H NMR δ3.33 (t, 4H, NCH2, J=6 Hz), 3.48 (t, 4H, OCH2, J=6 Hz), 4.43 (bs, 2H, OH), 7.57 (dd, 2H, H2+6, JH2, F3 and H6, F5=8.5 Hz, JH2, F5 and H6, F3=2Hz=22 Hz); 19F NMR δ −116.0 (d, 2F, F3+5, JF3, H2 and F5, 6=7.5 Hz); MS m/z 265 (M+Na+, 10), 243 (M+H+, 100), 211 (M-CH2OH, 85). Anal. (C11H12N2O2F2) C,H,N.

Workup

  1. customThe solvent was then evaporated
  2. customthe residue partitioned between CH2Cl2 (200 ml) and H2O (200 ml)
  3. dry with materialthe organic layer dried (MgSO4)
  4. customevaporated to dryness
  5. customThe residue was chromatographed
  6. customto give
  7. customafter recrystallization from toluene, 2.7 g (35%) of pure white crystals

Sources & evidence

ORD record
ord-c0611c5f8c5b4b40ae10354cd46eeab6
Source dataset
uspto-grants-2005_02
Patent number
US06852755B1

Reaction notes

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