Hydrochloric Acid → 3-(ethoxycarbonyl)-8-methyl-2-(trifluoromethyl)-2H-chromene-6-carboxylic acid

HRID 855110Notes

Reaction equation

HRID 855110 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:13])[C:11]=1[OH:12])[C:6]([OH:8])=[O:7])=O.C([O-])([O-])=O.[K+].[K+].C(N(CC)CC)C.[F:27][C:28]([F:37])([F:36])/[CH:29]=[CH:30]/[C:31]([O:33][CH2:34][CH3:35])=[O:32].Cl>CS(C)=O.CC(C)=O>[CH2:34]([O:33][C:31]([C:30]1[CH:29]([C:28]([F:27])([F:36])[F:37])[O:12][C:11]2[C:3]([CH:1]=1)=[CH:4][C:5]([C:6]([OH:8])=[O:7])=[CH:9][C:10]=2[CH3:13])=[O:32])[CH3:35]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoateHCID 865994903-Formyl-4-hydroxy-5-methylbenzoic acid

Product 1

HCID 695174193-(ethoxycarbonyl)-8-methyl-2-(trifluoromethyl)-2H-chromene-6-carboxylic acid

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-formyl-4-hydroxy-5-methylbenzoic acid (8.8 g, 48.89 mmole), K2CO3 (13.49 g, 97.78 mmole), triethylamine (19.79 g, 195.56 mmole), and ethyl 4,4,4-trifluorocrotonate (32.85 g, 195.56 mmole) in anhydrous DMSO (20.0 mL) was heated to 90° C. under a dry N2 atmosphere for 18 hrs. The mixture was then cooled, poured into 2.0 N HCl (100 ml), and extracted with EtOAc (2×100 mL). The combined extracts were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo to give an oily solid. Redissolved in acetone to givea white precipitat, which was filtered and dried on high vacuum (7.2 g, 51%). GCMS m/z 330.0 (M+). 1H NMR (DMSO/400 MHz) 12.99 (s, 1H), 8.11 (s, 1H), 8.06 (s, 1H), 7.94 (s, 1H), 6.19 (q, 1H, J=7.0 Hz), 4.35 (m, 2H), 2.31 (s, 3H), 1.36 (m, 3H).

Workup

  1. temperatureThe mixture was then cooled
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined extracts were washed with brine (100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oily solid
  8. filtrationwas filtered
  9. customdried on high vacuum (7.2 g, 51%)

Sources & evidence

ORD record
ord-0ed30349f05e423aa02780fb30775c83
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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