Diisopropylamine → 2-Fluoro-3-octyl-6-(4-octyloxyphenyl)pyridine

HRID 1780547Notes

Reaction equation

HRID 1780547 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:22][CH:21]=2)[N:15]=1.Br[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>O1CCCC1.CCCCCC.O>[F:13][C:14]1[C:19]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:18][CH:17]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:22][CH:21]=2)[N:15]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 81401-BromooctaneHCID 179115002-(4-Octyloxyphenyl)-6-fluoropyridineHCID 178418339Butyllithium

Product 1

HCID 190469322-Fluoro-3-octyl-6-(4-octyloxyphenyl)pyridineYield 3.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

0.74 g (7.3 mmol) of diisopropylamine in 30 ml of tetrahydrofuran is stirred at 0° C. with 4.56 ml (7.3 mmol) of a 1.6-molar n-butyllithium solution in hexane under argon for 1 hour. After cooling to -78° C., 2.00 g (6.64 mmol) of 2-fluoro-6-(4-octyloxyphenyl)pyridine in 30 ml of tetrahydrofuran are added dropwise at such a rate that the temperature does not exceed 70° C. After 4 hours at -78° C., 1.35 g (7.00 mmol) of 1-bromooctane in 10 ml of tetrahydrofuran are added dropwise while also maintaining a temperature ≤-70° C. The reaction mixture is stirred overnight, during which it warms to room temperature, 5 ml of water are added, and the mixture is evaporated to dryness. The residue is taken up in ether, the resulting solution is washed twice with water, the organic phase is dried over sodium sulfate, filtered, the solvent is distilled off, the residue is purified by chromatography (silica gel, 9:1 hexane/ethyl acetate) and recrystallized from acetonitrile, giving 0.10 g of 2-fluoro-3-octyl-6-(4-octyloxyphenyl)pyridine, whose physical properties are identical to those of the product prepared by Example 1.

Workup

  1. customdoes not exceed 70° C
  2. temperaturealso maintaining a temperature ≤-70° C
  3. customwarms to room temperature
  4. customthe mixture is evaporated to dryness
  5. washthe resulting solution is washed twice with water
  6. dry with materialthe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. distillationthe solvent is distilled off
  9. customthe residue is purified by chromatography (silica gel, 9:1 hexane/ethyl acetate)
  10. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-28d28a7ea4c741239408e610d360cdb4
Source dataset
uspto-grants-1997_05
Patent number
US05630962

Reaction notes

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