Tetrahydrofuran → (E)-ethyl 3-(1-(3,4-difluorophenyl)cyclohexyl)acrylate

HRID 71234Notes

Reaction equation

HRID 71234 reaction equation
C[C:2]([CH3:5])([O-:4])C.[K+].[F:7][C:8]1[CH:9]=[C:10]([C:15]2([CH:21]=O)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:11]=[CH:12][C:13]=1[F:14].C1C[O:26][CH2:25][CH2:24]1>CCOC(C)=O>[F:7][C:8]1[CH:9]=[C:10]([C:15]2(/[CH:21]=[CH:24]/[C:25]([O:4][CH2:2][CH3:5])=[O:26])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]2)[CH:11]=[CH:12][C:13]=1[F:14]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 23665647Potassium tert-butoxideHCID 86614756HCID 86614756, compound

Product 1

HCID 86688201(E)-ethyl 3-(1-(3,4-difluorophenyl)cyclohexyl)acrylateYield 45.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of triethyl phosphonoacetate (1.802 mL, 9.00 mmol) in THF (20 mL) at 0° C. was added 1M potassium t-butoxide (9.00 mL, 9.00 mmol) dropwise, and the mixture was stirred at the same temperature. After 15 mins, a solution of 1-(3,4-difluorophenyl)cyclohexanecarbaldehyde (1009 mg, 4.5 mmol) in 10 mL of THF was added, and the mixture was stirred at room temperature for 2 hrs. The mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, and evaporated to give an oily residue. The residue was purified by Combiflash (80 g silica gel) eluting with 5:95 EtOAc—hexane to give (E)-ethyl 3-(1-(3,4-difluorophenyl)cyclohexyl)acrylate (608 mg, 45.9% yield for 2 steps) as an oil. 1H NMR (400 MHz, CCl3D) δ ppm 6.98-7.16 (3H, m), 6.91 (1H, d, J=15.82 Hz), 5.60 (1H, d, J=16.26 Hz), 4.17 (2H, q, J=7.18 Hz), 1.83-2.06 (4H, m), 1.40-1.61 (6H, m), 1.27 (3H, t, J=7.03 Hz).

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hrs
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customto give an oily residue
  6. customThe residue was purified by Combiflash (80 g silica gel)
  7. washeluting with 5:95 EtOAc—hexane

Sources & evidence

ORD record
ord-5dab46aefc53444981b1007dc842de37
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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