Ammonium Chloride → HCID 21285527, compound

HRID 2231665Notes

Reaction equation

HRID 2231665 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][N:9]=1.[NH2:15][C:16]1[C:23]([CH3:24])=[CH:22][C:21](I)=[CH:20][C:17]=1[CH2:18][OH:19].[Cl-].[NH4+]>CCCCCC.O1CCCC1.[Cl-].[Zn+2].[Cl-].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:15][C:16]1[C:23]([CH3:24])=[CH:22][C:21]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH3:6])=[N:9][CH:10]=2)=[CH:20][C:17]=1[CH2:18][OH:19]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 27348955-Bromo-2-methoxypyridineHCID 54083854HCID 54083854, compoundHCID 178418339Butyllithium

Product 1

HCID 21285527HCID 21285527, compound

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

n-Butyllithium (33 cm3 of a 1.6M solution in n-hexane) was added to a stirred solution of 2-methoxy-5-bromopyridine (9.4g) in tetrahydrofuran (THF) (70 cm3) at -70° under nitrogen. After stirring for 1 hour at -70° the mixture treated with a solution of anhydrous zinc chloride (14.2 g) in THF (70 cm3) and the mixture was warmed to room temperature. 2-Amino-5-iodo-3-methylbenzyl alcohol (3.9 g--see preparation 8) and tetrakis(triphenylphosphine) palladium (0) (0.4 g) were added and the mixture heated under reflux for 3 hours. Saturated ammonium chloride solution (50 cm3) was added to the cooled solution and the mixture was partitioned between ethyl acetate (300 cm3) and a solution of ethylenediaminetetraacetic acid disodium salt (20 g) in water (300 cm3). The aqueous phase was further extracted with ethyl acetate (300 cm3) and the combined and dried (MgSO4) organic phases were evaporated in vacuo to give a brown oil which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with dichloromethane:methanol, 49:1. Combination and evaporation of appropriate fractions afforded the title compound as a waxy solid, m.p. 80°-82° (3.6 g), which was used directly without further purification.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 3 hours
  3. customthe mixture was partitioned between ethyl acetate (300 cm3)
  4. extractionThe aqueous phase was further extracted with ethyl acetate (300 cm3)
  5. dry with materialdried (MgSO4) organic phases
  6. customwere evaporated in vacuo
  7. customto give a brown oil which
  8. customwas chromatographed on silica (Merck "MK 60.9385" [Trade Mark])
  9. washeluting with dichloromethane
  10. customCombination and evaporation of appropriate fractions

Sources & evidence

ORD record
ord-53e7fa192e054244b57984a2b86e24d0
Source dataset
uspto-grants-1988_11
Patent number
US04783467

Reaction notes

Loading…