Ammonium Chloride → 2-[(2,5-Difluorophenyl)hydroxymethyl]-6-(1,3-dioxolan-2-yl)pyridine

HRID 2080371Notes

Reaction equation

HRID 2080371 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)[N:8]=1.[F:18][C:19]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:20]=1[CH:21]=[O:22].[Cl-].[NH4+]>O1CCCC1>[F:18][C:19]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:20]=1[CH:21]([OH:22])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)[N:8]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 1186132-Bromo-6-(1,3-dioxolan-2-yl)pyridineHCID 1376632,5-DifluorobenzaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 231147552-[(2,5-Difluorophenyl)hydroxymethyl]-6-(1,3-dioxolan-2-yl)pyridineYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere, a tetrahydrofuran solution (2.0M, 12.4 ml, 24.8 mmol) of isopropylmagnesium chloride was added dropwise to a tetrahydrofuran (20 ml) solution of 2-bromo-6-(1,3-dioxolan-2-yl)pyridine (2.7 ml, 24.8 mmol) under ice cooling. The reaction mixture was stirred at room temperature for 3 hours. To the resulting brown solution was added dropwise 2,5-difluorobenzaldehyde (2.7 ml, 24.8 mmol) under ice cooling. The temperature of the reaction mixture was raised gradually to room temperature and then, stirring was conducted for 16 hours. After a saturated aqueous solution of ammonium chloride was added, the resulting mixture was extracted with ethyl acetate. The extract was washed sequentially with water and brine. The organic layer thus obtained was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography. The fraction obtained from the hexane:ethyl acetate=4:1 eluate was concentrated under reduced pressure to give the title compound (2.90 g, 9.89 mmol, 40%) as a colorless oil.

Workup

  1. temperatureThe temperature of the reaction mixture was raised gradually to room temperature
  2. stirringstirring
  3. waitwas conducted for 16 hours
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe extract was washed sequentially with water and brine
  6. customThe organic layer thus obtained
  7. dry with materialwas dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe fraction obtained from the hexane
  10. concentrationethyl acetate=4:1 eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-377f860b0d2f41bab1e49b877150cc93
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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