Hydrochloric Acid → HCID 69517224, compound

HRID 854895Notes

Reaction equation

HRID 854895 reaction equation
[Cl:1][C:2]1[C:3]([OH:12])=[C:4]([CH:7]=[C:8]([O:10][CH3:11])[CH:9]=1)[CH:5]=O.C([O-])([O-])=O.[K+].[K+].[F:19][C:20]([F:29])([F:28])/[CH:21]=[CH:22]/[C:23]([O:25][CH2:26][CH3:27])=[O:24].Cl>CN(C=O)C>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:4]2[C:3]=1[O:12][CH:21]([C:20]([F:19])([F:29])[F:28])[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoateHCID 220401323-Chloro-2-hydroxy-5-methoxybenzaldehyde

Product 1

HCID 69517224HCID 69517224, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-chloro-2-hydroxy-5-methoxybenzaldehyde prepared as in Step 1 (9.00 g, 48.2 mmole), K2CO3 (6.67 g, 48.2 mmole) and ethyl 4,4,4-trifluorocrotonate (8.65 mL, 57.9 mmole) in anhydrous DMF (20 mL) under a dry N2 atmosphere was stirred at room temperature for 30 minutes and was then heated to 85° C. for 3 h. Additional ethyl 444-trifluorocrotonate (3.00 mL, 20.1 mmole) was then added and the mixture was stirred at 85° C. overnight. The mixture was then cooled and poured into 1 N HCl (200 mL). Following extraction with EtOAc (3×200 mL), the combined extracts were washed with 0.25 N NaOH until the washes were basic, brine, dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by crystallization from ethanol to give 11.0 g (68% yield) of the product as a yellow crystalline solid: 'H NMR (dmso-d6/300 MHz) 7.92 (s, 1H), 7.18 (d, 1H, J=2.8 Hz), 7.13 (d, 1H, J=2.8 Hz), 6.05 (q, 1H, J=7.3 Hz), 4.21-4.29 (m, 2H), 3.73 (s, 3H), 1.26 (t, 3H, J=7.1 Hz).

Workup

  1. temperaturewas then heated to 85° C. for 3 h
  2. stirringthe mixture was stirred at 85° C. overnight
  3. temperatureThe mixture was then cooled
  4. extractionextraction with EtOAc (3×200 mL)
  5. washthe combined extracts were washed with 0.25 N NaOH until the washes
  6. dry with materialbrine, dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by crystallization from ethanol

Sources & evidence

ORD record
ord-c62d9871ec0646c6ac0788e7470acf33
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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