Ammonium Chloride → HCID 58882938, compound

HRID 2364192Notes

Reaction equation

HRID 2364192 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1.[Cl-].[NH4+]>C1COCC1>[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]([C:7]2[CH:12]=[N:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)[OH:21])=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 680234-FluorobenzaldehydeHCID 27348955-Bromo-2-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 58882938HCID 58882938, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-65 °C

Procedure

A 2.5M solution of n-BuLi in THF (181 mL, 0.452 mol) was added slowly to a stirred solution of 5-bromo-2-(methyloxy)pyridine (85 g, 0.452 mol) in THF (500 mL) cooled to −65° C. The internal temperature was maintained at or below −55° C. during the addition; when the addition was complete, a solution of 4-fluorobenzaldehyde (51 g, 0.411 mol) in THF (120 mL) was added slowly maintaining the temperature at or below −50° C. Saturated ammonium chloride solution (200 mL) was added and the mixture was warmed to −15° C. and concentrated at reduced pressure. The mixture was diluted with EtOAc (1 L) and washed twice with saturated ammonium chloride solution. The aqueous layers were back-extracted with EtOAc and the combined organic layers were washed with brine, dried and concentrated to afford the product as a light amber oil: 1H NMR (CDCl3) δ 8.14 (1H, d, J=2.5 Hz), 7.54 (1H, dd, J=8.6, 2.5 Hz), 7.36 (2H, dd, J=8.6, 5.4 Hz), 7.05 (2H, m), 6.73 (1H, d, J=8.6 Hz), 5.82 (1H, s), 3.94 (3H, s), 2.40 (1H, br).

Workup

  1. temperatureThe internal temperature was maintained at or below −55° C.
  2. additionduring the addition
  3. additionwhen the addition
  4. temperaturemaintaining the temperature at or below −50° C
  5. temperaturethe mixture was warmed to −15° C.
  6. concentrationconcentrated at reduced pressure
  7. additionThe mixture was diluted with EtOAc (1 L)
  8. washwashed twice with saturated ammonium chloride solution
  9. extractionThe aqueous layers were back-extracted with EtOAc
  10. washthe combined organic layers were washed with brine
  11. customdried
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-3abf027a01c24ee59f21b6507dd2a33a
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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