Methyl Acrylate → HCID 12273592, compound

HRID 626948Notes

Reaction equation

HRID 626948 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]1(=[O:19])[CH2:18][CH2:17][CH2:16][CH:15]=[CH:14]1.[C:20]([O:24][CH3:25])(=[O:23])[CH:21]=[CH2:22].[Cl-].[NH4+]>CCOCC.C1COCC1>[O:19]=[C:13]1[CH2:18][CH:17]2[CH2:16][CH2:15][CH:14]1[CH2:22][CH:21]2[C:20]([O:24][CH3:25])=[O:23]

Participants

8

Reactant 5

HCID 7294Methyl AcrylateHCID 7912DiisopropylamineHCID 135942-Cyclohexen-1-oneHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 12273592HCID 12273592, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-11 °C

Procedure

To a cooled solution of diisopropylamine (7.72 mL, 54.62 mmol) in ether (40 mL) at −78° C. was added 2.5M n-butyllithium (21.8 mL) dropwise. The reaction mixture was allowed to warm to −11° C. A solution of cyclohex-2-en-1-one (5.04 mL, 52.01 mmol) in diethyl ether (60 mL) was added over 45 minutes. During the addition, the temperature was maintained between −11° C. and −3° C. The mixture was stirred for an additional 25 minutes before a solution of methyl prop-2-enoate (4.68 mL, 52.01 mmol) in THF (40 mL) was added dropwise over 60 minutes. The reaction mixture was stirred at this temperature for 1 h and stored in a freezer overnight. The reaction mixture was poured into saturated ammonium chloride solution (200 mL) and stirred for 15 minutes. A brown sticky polymer was formed and removed using tweezers. The organic layer was separated and the aqueous layer was extracted with tert-butyl methyl ether (2×300 mL). The combined organic layers were dried over sodium sulfate and concentrated. The crude residue was purified by column chromatography (Biotage; 0-60% ethyl acetate in heptane) in 2 batches, to afford the title compound (2.98 g, 31%) as the trans isomer as a clear colourless liquid. δH (500 MHz, CDCl3) 3.70 (s, 3H), 2.76 (ddt, J 10.6, 6.4, 1.8 Hz, 1H), 2.53-2.48 (m, 1H), 2.47-2.38 (m, 1H), 2.37-2.31 (m, 1H), 2.22 (ddt, J 14.2, 6.3, 2.5 Hz, 1H), 2.13 (ddd, J 19.1, 2.9, 1.8 Hz, 1H), 2.02 (ddd, J 14.3, 11.0, 3.5 Hz, 1H), 1.89-1.74 (m, 3H), 1.70-1.60 (m, 1H).

Workup

  1. additionDuring the addition
  2. temperaturethe temperature was maintained between −11° C. and −3° C
  3. additionwas added dropwise over 60 minutes
  4. waitstored in a freezer overnight
  5. stirringstirred for 15 minutes
  6. customA brown sticky polymer was formed
  7. customremoved
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with tert-butyl methyl ether (2×300 mL)
  10. dry with materialThe combined organic layers were dried over sodium sulfate
  11. concentrationconcentrated
  12. customThe crude residue was purified by column chromatography (Biotage; 0-60% ethyl acetate in heptane) in 2 batches

Sources & evidence

ORD record
ord-36c6335370f84060b4380d5f2996dab8
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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