Vanillin → Ethyl 3-methyl-4-(4-formyl-2-methoxyphenoxy)-2-butenoate

HRID 543340Notes

Reaction equation

HRID 543340 reaction equation
[O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.[H-].[Na+].Br[CH2:15][C:16]([CH3:23])=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].[OH-].[Na+]>CN(C=O)C.CCOCC>[CH3:15][C:16]([CH2:23][O:9][C:8]1[CH:10]=[CH:11][C:3]([CH:2]=[O:1])=[CH:4][C:5]=1[O:6][CH3:7])=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

7

Reactant 4

HCID 1183VanillinHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 53411540Ethyl-4-bromo-3-methyl-but-2-enoate (E/Z; 55/45)

Product 1

HCID 54099897Ethyl 3-methyl-4-(4-formyl-2-methoxyphenoxy)-2-butenoate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent3×

Procedure

Vanillin (3.43 g, 22.5 mmol) in 10 ml of DMF is added portionwise, at 0°, to sodium hydride (21.5 g, 23.6 mmol) in ml of DMF. The mixture is stirred for 10 min. and then ethyl 4-bromo-3-methyl-2-butenoate (4.87 g, 23.5 mmol) in 3 ml of DMF is added. After 3 hours, the reaction mixture is poured into ether and 5% sodium hydroxide solution. The aqueous layer is extracted with ether, and the organic layers are combined and washed with 5% sodium hydroxide, with water and with brine and dried. Solvent is removed in vacuo and the crude product is chromatographed to give ethyl 3-methyl-4-(4-formyl-2-methoxyphenoxy)-2-butenoate. To isopropyltriphenylphosphonium iodide (2.26 g, 5.23 mmol) in 15 ml of tetrahydrofuran (THF) is added n-butyllithium (1.6 M; 3.10 ml, 5.0 mmol) at -5°. The mixture is cooled to -60°, and ethyl 3-methyl-4-(4-formyl-2-methoxyphenoxy)-2-butenoate (0.70 g, 2.51 mmol) in 10 ml of THF is added. After 45 min. the reaction mixture is poured into ether and water, and the aqueous phase is extracted with ether. The combined ether layers are washed with water and with brine and dried. Solvent is removed in vacuo, and the crude product is triturated with hexane and the hexane-soluble fraction is purified by prep. TLC to give ethyl 3-methyl-4-[2-methoxy-4-(2-methyl-1-propenyl)phenoxy]-2-butenoate, MS m/e 304 (M+).

Workup

  1. waitAfter 3 hours
  2. extractionThe aqueous layer is extracted with ether
  3. washwashed with 5% sodium hydroxide, with water and with brine
  4. customdried
  5. customSolvent is removed in vacuo
  6. customthe crude product is chromatographed

Sources & evidence

ORD record
ord-f89dbe30299a48088a96a06045b70f3b
Source dataset
uspto-grants-1987_04
Patent number
US04661617

Reaction notes

Loading…