N,N-Diethylaniline → Methyl 4-hydroxy-3-(1-vinylcyclopentyl)benzoate

HRID 404389

Reaction equation

HRID 404389 reaction equation
C1(=CC[O:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)CCCC1.C(N(CC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)C.[CH3:30]/C(/O[Si](C)(C)C)=N\[Si](C)(C)C>C(OCC)C>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:17][C:18]=1[C:26]1([CH:27]=[CH2:22])[CH2:25][CH2:24][CH2:23][CH2:30]1

Participants

5

Reactant 3

HCID 7061N,N-DiethylanilineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 57467652Methyl 4-(2-cyclopentylideneethoxy)benzoate

Product 1

HCID 57467653Methyl 4-hydroxy-3-(1-vinylcyclopentyl)benzoateYield 30.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
240 °C

Procedure

The reaction mixture of methyl 4-(2-cyclopentylideneethoxy)benzoate 26.2 (0.50 g, 2.0 mmol), N,N-diethylaniline (3.2 mL, 20 mmol) and N,O-bis(trimethylsilyl)acetamide (2.5 mL, 10 mmol) in a 20 mL seal tube was heated at 240° C. for 48 hours. The reaction was then cooled to room temperature. Diethyl ether (60 mL) was added, and the organic layer was washed with HCl (3N, 20 mL). The organic layer was separated and the solvent was removed. The residue was dissolved in MeOH (10 mL) and HCl (3N, 2 mL) and stiffed at room temperature for 30 minutes. Diethyl ether (80 mL) was added, and the organic layer was washed with NaHCO3 (30 mL) and brine (15 mL). The organic layer was dried over MgSO4. After filtration, the solvent was removed, and the residue was purified by CombiFlash® silica gel column chromatography, eluting with hexane/EtOAc, 95/5 to give 26.3 (0.15 g, yield 30%). 1H NMR (500 MHz, CDCl3) δ ppm 7.90 (1H, d, J=2.2 Hz), 7.80 (1H, dd, J=8.3, 2.0 Hz), 6.81 (1H, d, J=8.3 Hz), 5.99 (1H, dd, J=17.6, 10.5 Hz), 5.77 (1H, s), 5.18 (1H, dd, J=10.5, 1.0 Hz), 5.08 (1H, d, J=17.6 Hz), 3.82 (3H, s), 1.89-2.03 (4H, m), 1.56-1.78 (4H, m). MS ESI (neg.) m/e: 245.1 (M−H)+.

Workup

  1. customseal tube
  2. temperatureThe reaction was then cooled to room temperature
  3. washthe organic layer was washed with HCl (3N, 20 mL)
  4. customThe organic layer was separated
  5. customthe solvent was removed
  6. dissolutionThe residue was dissolved in MeOH (10 mL)
  7. additionDiethyl ether (80 mL) was added
  8. washthe organic layer was washed with NaHCO3 (30 mL) and brine (15 mL)
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationAfter filtration
  11. customthe solvent was removed
  12. customthe residue was purified by CombiFlash® silica gel column chromatography
  13. washeluting with hexane/EtOAc, 95/5

Sources & evidence

ORD record
ord-4a9bd7ebdd48484a98d468d14f5d1049
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Linked notes

Loading…