Citric Acid → 6-Chloro-2-fluoro-3-(pivalamidomethyl)benzoic acid

HRID 1469710Notes

Reaction equation

HRID 1469710 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[C:6]([F:13])[C:5]([CH2:14][NH:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:4][CH:3]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CO.O>[Cl:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([F:13])[C:5]([CH2:14][NH:15][C:16](=[O:21])[C:17]([CH3:19])([CH3:18])[CH3:20])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 58483442Ethyl 6-chloro-2-fluoro-3-(pivalamidomethyl)benzoate

Product 1

HCID 584833746-Chloro-2-fluoro-3-(pivalamidomethyl)benzoic acidYield 76.7%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of ethyl 6-chloro-2-fluoro-3-(pivalamidomethyl)benzoate (100 mg, 0.317 mmol) in THF:MeOH:H2O (3:2:1; 6 mL) was added NaOH (25 mg, 0.634 mmol). The reaction mass was stirred at rt for 3 h. The reaction mass was neutralized with citric acid and concentrated. The residue was diluted with EtOAc and was washed with water and brine. The organic layer was separated, dried, filtered and concentrated to afford 70 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 14.10 (s, 1H), 8.14 (br t, 1H), 7.38-7.26 (m, 2H), 4.25 (d, J=5.4 Hz, 2H), 1.11 (s, 9H).

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with EtOAc
  3. washwas washed with water and brine
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-16a8d297a87244c49822f746c5a96586
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

Loading…