Ethanol → 3.5-Difluoro-4-[bis(2-hydroxyethyl)amino]benzoic acid

HRID 23609Notes

Reaction equation

HRID 23609 reaction equation
[F:1][C:2]1[CH:3]=C([CH:7]=[C:8]([F:17])[C:9]=1[N:10]([CH2:14][CH2:15][OH:16])[CH2:11][CH2:12][OH:13])C#N.[OH-:18].[Na+].[CH2:20]([OH:22])[CH3:21]>>[F:1][C:2]1[CH:3]=[C:21]([CH:7]=[C:8]([F:17])[C:9]=1[N:10]([CH2:14][CH2:15][OH:16])[CH2:11][CH2:12][OH:13])[C:20]([OH:18])=[O:22]

Participants

4

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 225901583,5-Difluoro-4-[bis(2-hydroxyethyl)amino]benzonitrile

Product 1

HCID 113344793.5-Difluoro-4-[bis(2-hydroxyethyl)amino]benzoic acidYield 87%

Procedure

A solution of the 3.5-Difluoro-4-[bis(2-hydroxyethyl) amino]benzonitrile (3.15 g, 13 mmol) and NaOH (5.2 g, 0.13 mol) in aqueous ethanol (65 ml, 50%) was refluxed for 2.5 hours. The solution was then partitioned between EtOAc (800 ml) and HCl (330 ml, 0.4 M), the aqueous layer washed with EtOAc (3×150 ml), the combined organic layers dried (MgSO4) and evaporated to dryness. The solid recrystallized from EtOAc (100 ml) to give 2.94 g (87%) of pure white crystals: mp 146.5-150° C.; 1H NMR δ 3.3 (t, 4H, CH2N), 3.46 (q, 4H, CH2O, J=5.5 Hz), 4.49 (t, 2H, OH, J=5 Hz), 7.44 (d, 2H, H2+6, J=10.5 Hz), 13.1 (bs, 1H, CO2H); 19F NMR δ −117.3 (d, 2F, F3+5, J=9.5 Hz); MS m/z 284 (M+Na+, 15), 262 (M+H+, 100), 230 (M-CH2OH, 40). Anal. (C11H13NO4F2) C,H,N.

Workup

  1. customThe solution was then partitioned between EtOAc (800 ml) and HCl (330 ml, 0.4 M)
  2. washthe aqueous layer washed with EtOAc (3×150 ml)
  3. dry with materialthe combined organic layers dried (MgSO4)
  4. customevaporated to dryness
  5. customThe solid recrystallized from EtOAc (100 ml)

Sources & evidence

ORD record
ord-8720b881df16442ea2b6424643b02e5e
Source dataset
uspto-grants-2005_02
Patent number
US06852755B1

Reaction notes

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