Potassium Hydroxide → HCID 15614965, compound

HRID 620371Notes

Reaction equation

HRID 620371 reaction equation
C1C=CN=CC=1.[FH:7].N[C:9]1[C:10]([CH3:25])=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]([C:19]([F:22])([F:21])[F:20])=[C:14]([O:23][CH3:24])[CH:13]=[CH:12]2.[OH-].[K+].N([O-])=O.[Na+]>N1C=CC=CC=1>[F:7][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:23][CH3:24])[C:15]=2[C:19]([F:22])([F:21])[F:20])[C:10]=1[CH3:25]

Participants

6

Reactant 4

HCID 14797Potassium HydroxideHCID 64774Pyridine, hydrofluoride (1:1)2×HCID 15614969HCID 15614969, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 15614965HCID 15614965, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-78 °C

Procedure

A 250 mL nalgene bottle with magnetic stir bar under an N2 atmosphere was charged with HF-pyridine (70%-30% by weight) (75 mL) and cooled to -78° C. in a dry ice-isopropanol bath. When the HF-pyridine solution was frozen, a solution of the 6-amino-2-methoxy-5-methyl-1-trifluoromethylnaphthalene (10.07 g, 39.4 mmol) in pyridine (25 mL, previously dried over KOH) was added slowly. Again, when the solution was frozen, solid sodium nitrite (4.55 g, 1.67 eq) was added and the dry ice-isopropanol bath was removed. The reaction mixture was stirred at room temperature for 30 minutes (after 10 minutes the frozen solids had melted). The reaction mixture wass then heated in a 65° C. oil bath for 2 hours. During the heating period a foamy precipitate had collected in the reaction vessel. The reaction mixture was cooled to room temperature and added to water (1 L). The aqueous phase was extracted with ether (3×300 mL). The combined ether extracts were washed with saturated aqueous NaCl (200 mL). Silica gel (40 mL) was added to the ether phase and the ether was removed. The silica absorbate was flash chromatographed (95:5 petroleum ether:ethyl acetate) to provide the white solid product (7.82 g, 77%), m.p. 97°-99° C.

Workup

  1. additionwas added slowly
  2. temperatureAgain, when the solution was frozen
  3. customthe dry ice-isopropanol bath was removed
  4. temperatureThe reaction mixture wass then heated in a 65° C. oil bath for 2 hours
  5. customDuring the heating period a foamy precipitate had collected in the reaction vessel
  6. temperatureThe reaction mixture was cooled to room temperature
  7. additionadded to water (1 L)
  8. extractionThe aqueous phase was extracted with ether (3×300 mL)
  9. washThe combined ether extracts were washed with saturated aqueous NaCl (200 mL)
  10. additionSilica gel (40 mL) was added to the ether phase
  11. customthe ether was removed
  12. customchromatographed (95:5 petroleum ether:ethyl acetate)

Sources & evidence

ORD record
ord-95f254c84ed54b92880bd5632427bd85
Source dataset
uspto-grants-1989_04
Patent number
US04820727

Reaction notes

Loading…