Trifluoromethanesulfonic anhydride → methyl 8-bromo-2-morpholino-4-oxo-4H-chromene-6-carboxylate

HRID 1187174Notes

Reaction equation

HRID 1187174 reaction equation
FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[Br:16][C:17]1[CH:18]=[C:19]([CH:24]=[C:25]([C:28](=[O:38])[CH2:29][C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[O:31])[C:26]=1O)[C:20]([O:22][CH3:23])=[O:21]>ClCCCl>[Br:16][C:17]1[CH:18]=[C:19]([C:20]([O:22][CH3:23])=[O:21])[CH:24]=[C:25]2[C:26]=1[O:31][C:30]([N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)=[CH:29][C:28]2=[O:38]

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydrideHCID 58235040Methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate

Product 1

HCID 58234996methyl 8-bromo-2-morpholino-4-oxo-4H-chromene-6-carboxylateYield 50.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

Trifluoromethanesulfonic anhydride (0.755 L, 4487 mmol) was added to a stirred solution of methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate (433 g, 1122 mmol, pooled material from several batches) dissolved in 1,2-dichloroethane (1 L) at RT under nitrogen (exotherm). The resulting solution was stirred at 50° C. overnight. The mixture was partially evaporated, and the residue was diluted with MeOH (1.6 L) at 0° C. (exotherm) and stirred for 1 hr at RT. The solvent was evaporated again and the residue was diluted in DCM, quenched with a saturated aqueous solution of sodium carbonate and extracted with DCM. The combined organic phases were washed with brine, dried over magnesium sulfate and concentrated to afford the crude product. The crude was triturated under MTBE (2×), ethyl acetate (1×) and MTBE (1×). The solid was dried to afford methyl 8-bromo-2-morpholino-4-oxo-4H-chromene-6-carboxylate (208 g, 50%) as a beige solid. Mass Spectrum: M+H+ 370.

Workup

  1. customThe mixture was partially evaporated
  2. additionthe residue was diluted with MeOH (1.6 L) at 0° C. (exotherm)
  3. stirringstirred for 1 hr at RT
  4. customThe solvent was evaporated again
  5. additionthe residue was diluted in DCM
  6. customquenched with a saturated aqueous solution of sodium carbonate
  7. extractionextracted with DCM
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customto afford the crude product
  12. customThe crude was triturated under MTBE (2×)
  13. customThe solid was dried

Sources & evidence

ORD record
ord-28877ead431e4ad8aba4d45a36ad19a2
Source dataset
uspto-grants-2014_03
Patent number
US08673906B2

Reaction notes

Loading…