Diisopropylamine → (3-Fluorophenyl)-(3-fluoropyridin-4-yl)-methanol

HRID 34004

Reaction equation

HRID 34004 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[F:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH:24]=[O:25].[Cl-].[NH4+]>O1CCCC1.CCCCCC.C(OCC)(=O)C>[F:20][C:21]1[CH:22]=[C:23]([CH:24]([C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[F:13])[OH:25])[CH:26]=[CH:27][CH:28]=1

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 677943-FluoropyridineHCID 680093-FluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 23070104(3-Fluorophenyl)-(3-fluoropyridin-4-yl)-methanol

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen atmosphere, a solution of 6.1 mL of diisopropylamine in 100 ml of dehydrated tetrahydrofuran was cooled to −70° C., added with 28 mL of 1.56 M n-butyllithium in hexane, and stirred at 0° C. for 15 minutes. After cooling to −70° C., 3.4 mL of 3-fluoropyridine was added dropwise, stirred at the same temperature for 4 hours, and then added dropwise with 4.8 mL of 3-fluorobenzaldehyde. After stirring for 1 hour, aqueous ammonium chloride and ethyl acetate were successively added, and the reaction solution was recovered to room temperature. The organic layer was extracted, washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting residue was recrystallized from diisopropyl ether, to afford 7.1 g of the title compound as colorless cubic crystals.

Workup

  1. temperatureAfter cooling to −70° C.
  2. stirringstirred at the same temperature for 4 hours
  3. stirringAfter stirring for 1 hour
  4. customthe reaction solution was recovered to room temperature
  5. extractionThe organic layer was extracted
  6. washwashed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated
  9. customthe resulting residue was recrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-d9e6388343e342d9824144a604857359
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Linked notes

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