Ammonium Chloride → 1-Chloro-3-(4-fluorophenyl)-5-methylhex-5-en-3-ol

HRID 2036377Notes

Reaction equation

HRID 2036377 reaction equation
[Cl:1][CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)=[O:5].[NH4+].[Cl-].I[CH2:16][C:17]([CH3:19])=[CH2:18]>C1COCC1.[Zn]>[Cl:1][CH2:2][CH2:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([F:12])=[CH:10][CH:11]=1)([OH:5])[CH2:18][C:17]([CH3:19])=[CH2:16]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 676722-Chloro-4'-fluoropropiophenone2×HCID 108777523-Iodo-2-methylprop-1-ene2×

Product 1

HCID 596356741-Chloro-3-(4-fluorophenyl)-5-methylhex-5-en-3-olYield 76%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent4×

Procedure

A solution of 3-chloro-1-(4-fluorophenyl)-propan-1-one (18.6 g, 0.1 mol) in THF (50 mL) was added to a well-stirred suspension of zinc power (13 g, 0.2 mol) in a mixture of aqueous saturated NH4Cl solution (260 mL) and THF (65 mL). A solution of 3-iodo-2-methylprop-1-ene (36.4 g, 0.2 mol) in THF (50 mL) was added dropwise. The reaction mixture was mildly exothermic, and began to reflux spontaneously. After the refluxing had ceased, the mixture was stirred for 1 h. TLC showed the 3-chloro-1-(4-fluorophenyl)propan-1-one not reacted completely. A solution of 3-iodo-2-methylprop-1-ene (18.2 g, 0.1 mol) in THF (30 mL) was added, and the mixture was stirred at rt overnight. The mixture was extracted with EtOAc (2×500 mL). The combined organic layer was dried and concentrated. The residue was purified by column chromatography on silica gel eluted with petroleum ether/EtOAc 50:1→30:1→5:1, to give 1-chloro-3-(4-fluorophenyl)-5-methylhex-5-en-3-ol (17 g, yield 76%) as an oil.

Workup

  1. temperatureto reflux spontaneously
  2. customreacted completely
  3. stirringthe mixture was stirred at rt overnight
  4. extractionThe mixture was extracted with EtOAc (2×500 mL)
  5. customThe combined organic layer was dried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluted with petroleum ether/EtOAc 50:1→30:1→5:1

Sources & evidence

ORD record
ord-d79d496a32f74874b3e5481dd018b21b
Source dataset
uspto-grants-2013_11
Patent number
US08575157B2

Reaction notes

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