Triethylamine → ethyl (2E)-3-(3,5-difluoro-4-hydroxyphenyl)prop-2-enoate

HRID 1909515Notes

Reaction equation

HRID 1909515 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.C(N(CC)CC)C.[C:18]([O:22][CH2:23][CH3:24])(=[O:21])[CH:19]=[CH2:20].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.CN(C=O)C>[F:10][C:4]1[CH:3]=[C:2](/[CH:20]=[CH:19]/[C:18]([O:22][CH2:23][CH3:24])=[O:21])[CH:7]=[C:6]([F:8])[C:5]=1[OH:9]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 27362924-Bromo-2,6-difluorophenol

Product 1

HCID 59419838ethyl (2E)-3-(3,5-difluoro-4-hydroxyphenyl)prop-2-enoateYield 68.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a 350-mL pressure-tube was added 4-bromo-2,6-difluorophenol (23.82 g, 0.11 mol), triethylamine (55 mL, 0.39 mol), ethyl acrylate (34.27 g, 0.34 mol), DMF (50 mL), palladium (II) acetate (1.29 g, 5.75 mmol), and tri-o-tolyphosphine (2.34 g, 7.6 mmol) under N2. The mixture was sealed in the glass tube and was stirred at 110° C. overnight (21 hours). The reaction was cooled to room temperature and EtOAc (150 mL) was added. The mixture was stirred for 30 minutes, filtered through celite and rinsed with EtOAc (100 mL×3). The filtrate was acidified with 2N HCl to pH˜2. The organic layer was separated, and the aqueous layer was extracted with EtOAc (50 mL×2). The organic layers were combined and washed with water ((100 mL×2), brine (100 mL) and dried over sodium sulfate. After filtration, heptane (200 mL) was added and the solution was concentrated in vacuo. The resulting precipitate was filtered, washed with heptane (50 mL×2) and dried to afford the desired product (10) (17.09 g) as a light-yellow solid. The mother liquor was concentrated to obtain additional desired product (4.29 g) as a pale-yellow solid. 1H NMR (400 MHz, CDCl3) δ: 7.50 (d, J=15.9 Hz, 1H), 7.09 (d, J=8.3 Hz, 2H), 6.29 (d, J=15.9 Hz, 1H), 5.54 (br, 1H), 4.26 (q, J=7.1 Hz, 2H), 1.33 (t, J=7.1 Hz, 3H).

Workup

  1. customThe mixture was sealed in the glass tube
  2. temperatureThe reaction was cooled to room temperature
  3. stirringThe mixture was stirred for 30 minutes
  4. filtrationfiltered through celite
  5. washrinsed with EtOAc (100 mL×3)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with EtOAc (50 mL×2)
  8. washwashed with water ((100 mL×2), brine (100 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationAfter filtration, heptane (200 mL)
  11. additionwas added
  12. concentrationthe solution was concentrated in vacuo
  13. filtrationThe resulting precipitate was filtered
  14. washwashed with heptane (50 mL×2)
  15. customdried

Sources & evidence

ORD record
ord-5903d916d16a4f89a47be89de00b8581
Source dataset
uspto-grants-2013_12
Patent number
US08598374B2

Reaction notes

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