Triethyl phosphonoacetate → HCID 68191980, compound

HRID 1506286Notes

Reaction equation

HRID 1506286 reaction equation
C(OP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.CC(C)([O-])C.[K+].[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2([CH:34]=O)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1>C1COCC1>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2(/[CH:34]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 23665647Potassium tert-butoxideHCID 821264221-(4-Fluorophenyl)cyclohexanecarbaldehyde

Product 1

HCID 68191980HCID 68191980, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of ethyl 2-(diethoxyphosphoryl)acetate (0.714 mL, 3.57 mmol) in 10 mL of THF at 0° C. was added 1 M potassium tert-butoxide in THF (3.57 mL, 3.57 mmol) dropwise, and the mixture was stirred for 15 mins at the same temperature. Then a solution of 1-(4-fluorophenyl)cyclohexanecarbaldehyde (Intermediate I-7A, 368 mg, 1.784 mmol) in 3 mL of THF was added dropwise, and the mixture was stirred at room temperature for 18 hrs. The reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate extract was washed with brine, dried over sodium sulfate and evaporated to give an oily residue which was purified by Combiflash (80 g silica gel) eluting with hexane followed by 5:95 EtOAc-hexane to give the desired (E)-ethyl 3-(1-(4-fluorophenyl)cyclohexyl)acrylate (453 mg, 92% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.28 (2H, dd, J=9.02, 5.28 Hz), 7.01 (2H, t, J=8.80 Hz), 6.95 (1H, d, J=16.07 Hz), 5.60 (1H, d, J=16.07 Hz), 4.16 (2H, q, J=7.26 Hz), 1.99-2.08 (2H, m), 1.85-1.94 (2H, m), 1.39-1.62 (6H, m), 1.27 (3H, t, J=7.15 Hz).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hrs
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. extractionThe ethyl acetate extract
  4. washwas washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customto give an oily residue which
  8. customwas purified by Combiflash (80 g silica gel)
  9. washeluting with hexane

Sources & evidence

ORD record
ord-66f1b31a449348a982cc75ba5b7b76a8
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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