Ethyl 2-butynoate → (E)-3-(2,6-difluoro-3-methoxy-phenoxy)-but-2-enoic acid ethyl ester
Reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([F:10])[C:3]=1[OH:11].[CH2:12]([O:14][C:15](=[O:19])[C:16]#[C:17][CH3:18])[CH3:13].N12CCCN=C1CCCCC2>O1CCCC1>[CH2:12]([O:14][C:15](=[O:19])/[CH:16]=[C:17](/[O:11][C:3]1[C:4]([F:10])=[CH:5][CH:6]=[C:7]([O:8][CH3:9])[C:2]=1[F:1])\[CH3:18])[CH3:13]Participants
Procedure
To a stirred mixture of 2,6-difluoro-3-methoxy-phenol (5.00 g, 0.031 mol) and ethyl-2-butynoate (7.00 g, 0.062 mol) in tetrahydrofuran (40 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (4.76 g, 0.031 mol) in tetrahydrofuran (10 mL) slowly. After addition was complete the mixture was stirred at reflux overnight. Upon completion of the reaction the tetrahydrofuran was removed in vacuo and the residue was diluted in diethyl ether and washed first with 1N aqueous hydrochloric acid, then 10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and evaporated and the residue purified by ISCO column chromatography (Teledyne Isco RediSep Flash Column 120 g, 0% to 15%) ethyl acetate/hexanes which afforded (E)-3-(2,6-difluoro-3-methoxy-phenoxy)-but-2-enoic acid ethyl ester (6.42 g, 76%) as a colorless oil.
Workup
- additionAfter addition
- temperatureat reflux overnight
- customwas removed in vacuo
- additionthe residue was diluted in diethyl ether
- washwashed first with 1N aqueous hydrochloric acid
- dry with material10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate
- filtrationThe mixture was filtered
- customevaporated
- customthe residue purified by ISCO column chromatography (Teledyne Isco RediSep Flash Column 120 g, 0% to 15%) ethyl acetate/hexanes which
Sources & evidence
- ORD record
- ord-2cddb078f51c43a7951c6dc128202acb
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07741327B2
Reaction notes
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