Hexane → HCID 46233581, compound

HRID 1261382Notes

Reaction equation

HRID 1261382 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].N12CCN(CC1)CC2.[C:18]([O:22]CC)(=[O:21])[C:19]#[CH:20].CCCCCC>C(Cl)Cl.C(OCC)(=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[O:9]/[CH:20]=[CH:19]/[C:18]([OH:22])=[O:21]

Participants

7

Reactant 4

HCID 8058HexaneHCID 9237DabcoHCID 113352,6-DimethylphenolHCID 12182Ethyl propiolate

Product 1

HCID 46233581HCID 46233581, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(E)-3-(2,6-dimethylphenoxy)acrylic acid 30a was prepared by the general method of Fan, et al. ((2006 Synthesis 2286): ethyl (E/Z)-3-(2,6-dimethylphenoxy)acrylate: 2,6-Dimethylphenol (1.5 g, 12.3 mmol) and 1,4-diazabicyclo[2.2.2]octane (100 mg, 0.9 mmol) and 2 mL of methylene chloride were combined with magnetic stirring. Ethyl propiolate (1.2 mL, 12.6 mmol) in 3 mL of methylene chloride was added drop wise over 5-10 minutes. Thin-layer chromatography of the reaction mixture (silica gel, hexane) showed the formation of two products. The reaction mixture was diluted with ˜70 mL of ethyl acetate and extracted with 10% potassium hydroxide, and then with saturated sodium chloride solution. The mixture was then extracted with 10% hydrochloric acid solution and then again with saturated sodium chloride solution. The ethyl acetate extract was dried with anhydrous magnesium sulfate, filtered, and evaporated to dryness to afford 2.9 g (100%) of product. A sample of this material (1.0 g) was purified by normal-phase chromatography (COMBIFLASH) to afford 650 mg of ethyl (E)-3-(2,6-dimethylphenoxy)acrylate [1H NMR (400 MHz, CDCl3): 1.24 (t, 3H, J=7.2 Hz), 2.17 (s, 6H), 4.13 (q, 2H, J=7.2 Hz), 5.00 (d, 1H, J=12.4 Hz), 7.04 (m, 3H), 7.74 (d, 1H, J=12.4 Hz], and 300 mg of the ethyl (Z)-3-(2,6-dimethylphenoxy)acrylate [1H NMR (400 MHz, CDCl3): 1.31 (t, 3H, J=7.2 Hz), 2.24 (s, 6H), 4.23 (q, 2H, J=7.2 Hz), 5.02 (d, 1H, J=6.8 Hz), 6.46 (d, 1H, J=6.8 Hz), 7.02 (m, 3H)]. (E)-3-(2,6-Dimethylphenoxy)acrylic acid 30a. Three hundred milligrams of ethyl (E)-3-(2,6-dimethylphenoxy)acrylate was combined with 0.5 g of KOH in 10 mL of a 20:80 mixture of water/ethanol and heated at reflux for 2.5 hours. The progress of the reaction was monitored by thin-layer chromatography (silica gel, hexane/ethyl acetate, 95:5). When the reaction had gone to completion, the reaction mixture was removed from heat and the ethanol was removed under reduced pressure. The reaction mixture was acidified with 5% hydrochloric acid solution and extracted with three 30-mL portions of ethyl acetate. The ethyl acetate solution was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The solid that formed was titrated with hexane and collected by vacuum filtration to afford 100 mg of (E)-3-(2,6-dimethylphenoxy)acrylic acid 30a. NMR (400 MHz, CDCl3): 2.17 (s, 6H), 5.00 (d, 1H, J=12.4 Hz), 7.05 (s, 3H), 7.80 (d, 1H, J=12.4 Hz), 11.0 (br s, 1H). MS (ESI): 215 [M+Na]+.

Workup

  1. custom(2006 Synthesis 2286)
  2. extractionextracted with 10% potassium hydroxide
  3. extractionThe mixture was then extracted with 10% hydrochloric acid solution
  4. extractionThe ethyl acetate extract
  5. dry with materialwas dried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-6270be430b8944a0b9ab70982739d2f0
Source dataset
uspto-grants-2013_06
Patent number
US08470861B2

Reaction notes

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