Hydrochloric Acid → N-[4-Chloro-2-fluoro-5-(1-methylethoxy)phenyl]morpholine-3-carboxamide

HRID 263382

Reaction equation

HRID 263382 reaction equation
[Cl:1][C:2]1[C:8]([O:9][CH:10]([CH3:12])[CH3:11])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.C[Al](C)C.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH:19]1[C:24](O)=[O:25].Cl>C(Cl)Cl>[Cl:1][C:2]1[C:8]([O:9][CH:10]([CH3:11])[CH3:12])=[CH:7][C:5]([NH:6][C:24]([CH:19]2[CH2:20][O:21][CH2:22][CH2:23][NH:18]2)=[O:25])=[C:4]([F:13])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 158649Benzenamine, 4-chloro-2-fluoro-5-(1-methylethoxy)-HCID 33401523-Morpholinecarboxylic acidHCID 16682925Trimethylaluminum

Product 1

HCID 19037332N-[4-Chloro-2-fluoro-5-(1-methylethoxy)phenyl]morpholine-3-carboxamideYield 43.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 4-chloro-2-fluoro-5-(1-methylethoxy)aniline (15.52 g, 76.26 mmol) in CH2Cl2 (100 mL), under nitrogen at 0° C. (ice-bath) was added dropwise trimethylaluminum (114.4 mL, 228.78 mmol). The mixture was then stirred overnight at room temperature. 3-Morpholinecarboxylic acid (10.0 g, 76.20 mmol) was added portionwise at room temperature. The resultant reaction mixture was stirred at room temperature for 2 days. 6N HCl was added dropwise to the reaction mixture at 0° C. (ice-bath). The solid formed was filtered off and suspended in water (100 mL). The suspension was basicified with 50% aqueous NaOH to pH 13. 400 mL of CH2Cl2 was added. The organic layer was separated, dried over MgSO4 and the solvent was removed under vacuum to give the title compound of Step B as a white solid (10.5 g), m.p. 99°-101° C. 1H NMR: δ9.30 (br s,1H), 8.17 (d,1H), 7.14 (d,1H), 4.53 (q,1H), 3.96-3.61 (m,5H), 3.00-3.01 (m,2H), 1.37 (d,6H).

Workup

  1. customThe resultant reaction mixture
  2. stirringwas stirred at room temperature for 2 days
  3. customThe solid formed
  4. filtrationwas filtered off
  5. addition400 mL of CH2Cl2 was added
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-f7172ab3485646b5a13f32470cbcd42d
Source dataset
uspto-grants-1997_07
Patent number
US05643855

Linked notes

Loading…