Hydrochloric Acid → (E)-4-(1-(4-fluorophenyl)cyclohexyl)but-3-enoic acid

HRID 71242

Reaction equation

HRID 71242 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:14]=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Br-].[C:17]([CH2:20][CH2:21][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:19])=[O:18].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2(/[CH:14]=[CH:21]/[CH2:20][C:17]([OH:19])=[O:18])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 2733850(2-Carboxyethyl)triphenylphosphonium bromideHCID 821264221-(4-Fluorophenyl)cyclohexanecarbaldehyde

Product 1

HCID 66685187(E)-4-(1-(4-fluorophenyl)cyclohexyl)but-3-enoic acidYield 18.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred suspension of 1-(4-fluorophenyl)cyclohexanecarbaldehyde (160 mg, 0.776 mmol) and 2-carboxyethyl triphenylphosphonium bromide (483 mg, 1.164 mmol) in THF (7 mL) at −78° C. was added 1M lithium bis(trimethylsilyl)amide (2.172 mL, 2.172 mmol) in THF dropwise, and the mixture was stirred for 30 mins at −78° C., and 30 mins at a temperatures in the range of from −78° C. to room temperature. Next, the mixture was stirred overnight at room temperature. After addition of 3 mL of 1N HCl, the mixture was extracted with EtOAc (2×), and the combined extracts were washed with brine, dried over Na2SO4 and evaporated to give an oily residue. The residue was purified by Combiflash (24 g silica gel) eluting with 5:95 followed by 3:7 EtOAc-hexane to give (E)-4-(1-(4-fluorophenyl)cyclohexyl)but-3-enoic acid (37.7 mg, 0.144 mmol, 18.53% yield) along with the unreacted starting material (41.5 mg). 1H NMR (400 MHz, CCl3D) δ ppm 7.28-7.33 (2H, m), 6.93-6.99 (2H, m), 5.97 (1H, dt, J=11.64, 1.76 Hz), 5.58 (1H, dt, J=11.64, 7.25 Hz), 2.59 (2H, dd, J=7.25, 1.76 Hz), 1.86-1.96 (2H, m), 1.54-1.76 (8H, m), 1.22-1.33 (2H, m).

Workup

  1. custom30 mins
  2. customof from −78° C. to room temperature
  3. stirringNext, the mixture was stirred overnight at room temperature
  4. extractionthe mixture was extracted with EtOAc (2×)
  5. washthe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto give an oily residue
  9. customThe residue was purified by Combiflash (24 g silica gel)
  10. washeluting with 5:95

Sources & evidence

ORD record
ord-b96956f5f9574bf798c92aa95c1e7a7a
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Linked notes

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