Methanesulfonic Acid → HCID 21939646, compound

HRID 1242628Notes

Reaction equation

HRID 1242628 reaction equation
[OH:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14](=[O:16])[CH3:15])=[CH:4][CH:3]=1.[C:19]([C:23]([CH2:25][C:26](OCC)=[O:27])=O)([F:22])([F:21])[F:20].CS(O)(=O)=O.[OH-].[Na+]>O>[O:27]=[C:26]1[CH:25]=[C:23]([C:19]([F:22])([F:21])[F:20])[C:18]2[C:2](=[CH:3][CH:4]=[C:5]([CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:13][C:14](=[O:16])[CH3:15])[CH:17]=2)[O:1]1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 21939649HCID 21939649, compound

Product 1

HCID 21939646HCID 21939646, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

A solution of N-[2-(4-hydroxybenzyl)phenyl]acetamide (200 mg, 0.83 mmol) in CF3COCH2CO2Et (305 mg, 1.66 mmol) & MeSO3H (750 μL, 11.55 mmol) was heated at 75° C. for 2 d. On cooling to 20° C., the mixture was treated with H2O (20 mL), then the pH was adjusted to 12 with NaOH. The mixture was extracted with EtOAc (150 mL), then the extracts were washed with 0.5 M NaOH (2×50 mL), before being dried (MgSO4). Filtration, solvent evaporation, & column chromatography (1:2 PE-EtOAc) yielded N-[2-(2-oxo-4-trifluoromethyl-2H-chromen-6-ylmethyl)-phenyl]acetamide (78 mg, 26%): m/z (ES+)=362.2 [M+H]+. A solution of this compound in AcOH-12 M HCl (1:6, 3.5 mL) was heated at 95° C. for 6 h. On cooling to 20° C., H2O (8 mL) was added, then the mixture was treated with NaOH then Na2CO3 to adjust the pH to 10. Extraction with EtOAc (10 mL) & solvent evaporation furnished a residue which was subjected to column chromatography (2:1 PE-EtOAc) to give the title compound (8 mg, 12%): δH (CDCl3)=3.50 (br s, 2H), 4.00 (s, 2H), 6.70 (d, 1H), 6.80 (m, 2H), 7.00 (d, 1H), 7.10 (t, 1H), 7.35 (d, 1H), 7.40 (d, 1H), 7.55 (s, 1H); m/z (ES+)=320.1 [M+H]+. Compounds of Formula I

Workup

  1. extractionThe mixture was extracted with EtOAc (150 mL)
  2. washthe extracts were washed with 0.5 M NaOH (2×50 mL)
  3. dry with materialbefore being dried (MgSO4)
  4. filtrationFiltration, solvent evaporation, & column chromatography (1:2 PE-EtOAc)

Sources & evidence

ORD record
ord-553d8ac60c64457e89764b1be0d3fdc7
Source dataset
uspto-grants-2006_10
Patent number
US07115745B2

Reaction notes

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