Ethyl 2-butynoate → 3-(2-Fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester

HRID 19089Notes

Reaction equation

HRID 19089 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[OH:9].[CH2:10]([O:12][C:13](=[O:17])[C:14]#[C:15][CH3:16])[CH3:11].N12CCCN=C1CCCCC2>O1CCCC1.ClCCl>[CH2:10]([O:12][C:13](=[O:17])[CH:14]=[C:15]([O:9][C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[F:1])[CH3:16])[CH3:11]

Participants

6

Reactant 3

HCID 78043Ethyl 2-butynoateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 182387Phenol, 2-fluoro-5-methyl-

Product 1

HCID 668946653-(2-Fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl esterYield 52.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-fluoro-5-methyl-phenol (0.97 mL, 8.91 mmol) and ethyl-2-butynoate (2.0 g, 17.8 mmol) in tetrahydrofuran (13.7 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.33 mL, 8.91 mmol). The reaction was then heated at 130° C. for 4 h. At this time, the reaction was cooled to 25° C. and was stirred at 25° C. overnight. At this time, the reaction was diluted with dichloromethane (100 mL) and was washed with a 2N aqueous hydrochloric acid solution (1×100 mL), a 0.5N aqueous sodium hydroxide solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 2% ethyl acetate/hexanes) afforded 3-(2-fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester (1.12 g, 52%) as a clear oil: HR-ES-MS m/z calculated for C13H15O3F [M+H]+ 239.1078, observed 239.1078; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.12 (t, J=7.0 Hz, 3H), 2.30 (s, 3H), 2.43 (s, 3H), 4.00 (q, J=7.0 Hz, 2H), 4.69 (s, 1H), 7.01-7.19 (m, 2H), 7.30 (dd, J=10.7, 8.3 Hz, 1H).

Workup

  1. temperatureAt this time, the reaction was cooled to 25° C.
  2. washwas washed with a 2N aqueous hydrochloric acid solution (1×100 mL)
  3. dry with materialThe organics were then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by Analogix flash chromatography (40 g, 2% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0be8f9c5937645139c3c32ba535a6dca
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…