2-Chloro-4'-fluoropropiophenone → 1-Chloro-3-(4-fluorophenyl)hex-5-en-3-ol

HRID 470402

Reaction equation

HRID 470402 reaction equation
[CH2:1]([Mg]Br)[CH:2]=[CH2:3].[Cl:6][CH2:7][CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=[O:10]>C1COCC1>[Cl:6][CH2:7][CH2:8][C:9]([C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)([OH:10])[CH2:3][CH:2]=[CH2:1]

Participants

4

Reactant 2

HCID 676722-Chloro-4'-fluoropropiophenoneHCID 178455850HCID 178455850, compound

Product 1

HCID 534729381-Chloro-3-(4-fluorophenyl)hex-5-en-3-olYield 97.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 250-mL flask was charged with anhydrous CeCl3 (5.58 g, 22.6 mmol) and THF (40 mL). The mixture was vigorously stirred for 3.5 h at rt. The suspension was then cooled to −78° C. and a solution of allylmagnesium bromide (1.0 M in THF, 21 mL, 21.0 mmol) was added. After stirring for 2 h at −78° C., a solution of 3-chloro-1-(4-fluorophenyl)propan-1-one (2.522 g, 13.5 mmol) in THF (30 mL) was added via cannula. The reaction mixture was allowed to slowly warm to 8° C. while stirring overnight (18 h). The reaction was then quenched with satd aq NaHCO3, extracted with EtOAc, and dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/EtOAc to afford of 1-chloro-3-(4-fluorophenyl)hex-5-en-3-ol (3.0049 g, 97%) as an oil. LC-MS Method 1 tR=1.79 min, m/z 213, 211 (M-OH)+; 1H NMR (400 MHz, CDCl3) δ 7.37-7.32 (m, 2H), 7.07-7.02 (m, 2H), 5.57-5.47 (m, 1H), 5.20-5.19 (m, 1H), 5.16 (m, 1H), 3.59-3.52 (m, 1H), 3.24-3.18 (m, 1H), 2.70 (dd, J=13.8, 5.9 Hz, 1H), 2.50 (dd, J=13.8, 8.5 Hz, 1H), 2.29 (t, J=7.9 Hz, 2H), 2.22 (s, 1H); 19F NMR (376 MHz, CDCl3) δ −116.52 (m).

Workup

  1. temperatureThe suspension was then cooled to −78° C.
  2. stirringAfter stirring for 2 h at −78° C.
  3. temperatureto slowly warm to 8° C.
  4. stirringwhile stirring overnight (18 h)
  5. customThe reaction was then quenched with satd aq NaHCO3
  6. extractionextracted with EtOAc
  7. dry with materialdried over Na2SO4
  8. customAfter the solvents were evaporated
  9. customthe residue was purified by chromatography on silica gel
  10. washeluted with hexanes/EtOAc

Sources & evidence

ORD record
ord-0a30a34e67e547c08d2ef209b3170b6c
Source dataset
uspto-grants-2014_01
Patent number
US08629138B2

Linked notes

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