Ethyl Acetate → ethyl 3-(4-(3-(trifluoromethyl)phenyl)tetrahydro-2H-pyran-4-yl)acrylate

HRID 71256Notes

Reaction equation

HRID 71256 reaction equation
C(N(CC)C(C)C)(C)C.[Br-].[Li+].[F:12][C:13]([F:29])([F:28])[C:14]1[CH:15]=[C:16]([C:20]2([CH:26]=O)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:17]=[CH:18][CH:19]=1.[CH3:30][CH2:31][O:32][C:33]([CH3:35])=[O:34]>C1COCC1.Cl>[F:12][C:13]([F:29])([F:28])[C:14]1[CH:15]=[C:16]([C:20]2([CH:26]=[CH:35][C:33]([O:32][CH2:31][CH3:30])=[O:34])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 81531Diisopropylethylamine2×HCID 82050Lithium BromideHCID 42553290Tetrahydro-4-[3-(trifluoromethyl)phenyl]-2H-pyran-4-carboxaldehyde

Product 1

HCID 66685135ethyl 3-(4-(3-(trifluoromethyl)phenyl)tetrahydro-2H-pyran-4-yl)acrylateYield 92%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

N,N-diisopropylethylamine (2.95 mL, 16.9 mmol) and anhydrous lithium bromide (489 mg, 5.63 mmol) were added to a stirred solution of 4-(3-(trifluoromethyl)phenyl)-tetrahydro-2H-pyran-4-carbaldehyde (485 mg, 1.88 mmol) in THF (15 mL). After 20 min., triethyl phosphonoacetate (1.12 mL, 5.63 mmol) was added and the mixture was stirred at room temperature for 16 h. Additional N,N-diisopropylethylamine (980 μL, 5.64 mmol) was added and stirring was continued for additional 160 min. The reaction mixture was diluted with EtOAc and 1N aq. HCl solution. The organic layer was separated, washed with 1N aq. HCl solution, brine, dried (Na2SO4), filtered, and concentrated under vacuum to obtain a thin yellow oil which was chromatographed on silica gel (Teledyne-Isco RediSep 12 g column). Elution with 5%, 10%, and 20% EtOAc in hexanes afforded ethyl 3-(4-(3-(trifluoromethyl)phenyl)tetrahydro-2H-pyran-4-yl)acrylate (569 mg, 92% yield) as a viscous yellow oil. 1H NMR (400 MHz, CDCl3): δ ppm 7.38-7.68 (m, 4H), 6.98 (d, 1H), 5.71 (d, 1H), 4.19 (q, 2H), 3.76 (dd, 4H), 2.06-2.34 (m, 4H), 1.29 (t, 3H).

Workup

  1. stirringstirring
  2. waitwas continued for additional 160 min
  3. customThe organic layer was separated
  4. washwashed with 1N aq. HCl solution, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto obtain a thin yellow oil which
  9. customwas chromatographed on silica gel (Teledyne-Isco RediSep 12 g column)
  10. washElution with 5%, 10%, and 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-00917f15b5e14243a97b8046e4d882fe
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

Loading…