Hexane → HCID 60077543, compound

HRID 2084339Notes

Reaction equation

HRID 2084339 reaction equation
[Li]CCCC.CCCCCC.[F:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[O:20][CH3:21].Br/[CH:23]=[CH:24]\[C:25](OCC)=[O:26].CC(C[AlH]CC(C)C)C>C1COCC1.[Cl-].[Zn+2].[Cl-].CC([O-])=O.CC([O-])=O.[Pd+2]>[F:12][C:13]1[C:14]([O:20][CH3:21])=[C:15](/[CH:23]=[CH:24]\[CH2:25][OH:26])[C:16]([F:19])=[CH:17][CH:18]=1

Participants

9

Reactant 5

HCID 8058HexaneHCID 14487Diisobutylaluminum hydrideHCID 643842Ethyl cis-3-bromoacrylateHCID 27249892,5-DifluoroanisoleHCID 178418339Butyllithium

Product 1

HCID 60077543HCID 60077543, compoundYield 92.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of BuLi (2.5M) in hexane (9.6 ml; 0.024 mol) was added to a stirred solution of 2,5-difluoroanisol (2.88 g, 0.02 mol) in dry THF (30 ml) at −70C., followed after 2 h by solution of zinc chloride (3.6 g; 0.026 mol) in dry THF (50 ml). The reaction temperature was allowed to raise to room temperature and then stirring was maintained at room temperature for 30 min. Pd(OAc)2 (8 mg; 0.2 mol %) was added, followed by ethyl cis-3-bromoacrylate (3.58 g; 0.02 mol). The reaction mixture was placed in preheated oil bath and heated under reflux for 1 h. The resulting reaction mixture was chilled to −78 C and 60 ml (0.06 mol) of DIBAL (1 M solution in hexanes) was added dropwise. The stirring was continued at −78 C for 2 h and 1 h at room temperature. The reaction was quenched with water and all solids were dissolved by addition of HCl. The organic phase was diluted with ether, separated, washed with 5N HCl, brine and evaporated in vacuo. The residue was Kugelrohr distilled (1.5×10−2 mbar, 150 C) to give 3.7 g (92%) of crude (2Z)-3-(3,6-difluoro-2-methoxyphenyl)-2-propen-1-ol, which contains ˜6% of other regioisomers. The crude product was used in the next step without further purification. 1H-NMR (CDCl3): 7.00 (m, 1H); 6.77 (m, 1H); 6.31 (app. d, 1H); 6.12 (app. dt, 1H); 4.08 (br. t, 2H); 3.89 (d, 3H); 1.80 (br. t, 1H).

Workup

  1. temperaturewas maintained at room temperature for 30 min
  2. customThe reaction mixture was placed in preheated oil bath
  3. temperatureheated
  4. temperatureunder reflux for 1 h
  5. customThe resulting reaction mixture
  6. additionwas added dropwise
  7. customThe reaction was quenched with water
  8. dissolutionall solids were dissolved by addition of HCl
  9. additionThe organic phase was diluted with ether
  10. customseparated
  11. washwashed with 5N HCl, brine
  12. customevaporated in vacuo
  13. distillationdistilled (1.5×10−2 mbar, 150 C)

Sources & evidence

ORD record
ord-fa6f6b48b127462bab3cf172a8f10e22
Source dataset
uspto-grants-2004_04
Patent number
US06716850B2

Reaction notes

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