Hydrochloric Acid → 2-(4-Bromo-phenyl)-3-cyclohexyl-acrylic acid ethyl ester

HRID 2103631Notes

Reaction equation

HRID 2103631 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br-].[CH:12]1([CH2:18][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.[CH2:38]([O:40][C:41](=[O:51])[C:42]([C:44]1[CH:49]=[CH:48][C:47]([Br:50])=[CH:46][CH:45]=1)=O)[CH3:39].Cl>C1COCC1.O>[CH2:38]([O:40][C:41](=[O:51])[C:42]([C:44]1[CH:49]=[CH:48][C:47]([Br:50])=[CH:46][CH:45]=1)=[CH:18][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH3:39]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 10729811Ethyl 2-(4-bromophenyl)-2-oxoacetateHCID 20068889(Cyclohexylmethyl)triphenylphosphonium bromide

Product 1

HCID 670844132-(4-Bromo-phenyl)-3-cyclohexyl-acrylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Add LHMDS in THF (451 mL, 1.0 M, 451 mmol) to a slurry of cyclohexylmethyl-triphenyl-phosphonium bromide (207.5 g, 472 mmol) in THF (500 mL) maintained at 0 ° C. and stir the mixture for 1 h. Dissolve (4-bromo-phenyl)-oxo-acetic acid ethyl ester (prepared as described by Hu, Shengkui; Neckers, Douglas C. J. Org. Chem. 1996, 61, 6407-6415.) in THF (40 mL) and add the resulting solution to the reaction mixture. Stir the reaction mixture for 60 h at room temperature. Dilute the mixture with water and neutralize with 1 N HCl. Evaporate the THF and add ether (700 mL). Stir at room temperature for 30 minutes and filter through celite®. Separate the layers and extract the aqueous layers with ether. Dry the combined organic layers over magnesium sulfate, filter, and concentrate. If large amounts of triphenylphosphine oxide are present, add ether (1 L), filter through celite® and concentrate the filtrate. Dissolve the brown oil in CH2Cl2 (50 mL) and filter through a pad of silica gel, eluting with a gradient of 0-5% EtOAc in hexanes to obtain the title compound (109.7 g) as an E/Z mixture (E/Z ratio: 2/1). MS (m/e): 337 (+H).

Workup

  1. stirringStir the reaction mixture for 60 h at room temperature
  2. customEvaporate the THF
  3. additionadd ether (700 mL)
  4. stirringStir at room temperature for 30 minutes
  5. filtrationfilter through celite®
  6. customSeparate the layers
  7. extractionextract the aqueous layers with ether
  8. dry with materialDry the combined organic layers over magnesium sulfate
  9. filtrationfilter
  10. concentrationconcentrate
  11. additionadd ether (1 L)
  12. filtrationfilter through celite®
  13. concentrationconcentrate the filtrate
  14. dissolutionDissolve the brown oil in CH2Cl2 (50 mL)
  15. filtrationfilter through a pad of silica gel
  16. washeluting with a gradient of 0-5% EtOAc in hexanes

Sources & evidence

ORD record
ord-9aeb14643ecd4ff8bebe454fc3961d10
Source dataset
uspto-grants-2009_08
Patent number
US07576108B2

Reaction notes

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