Hydrochloric Acid → (7-Chloroquinolin-4-yl)methanol

HRID 1953453Notes

Reaction equation

HRID 1953453 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[C]=O.[BH4-].[Na+].Cl.[C:18](=O)(O)[O-:19].[Na+]>CO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C.C(N(CC)CC)C>[OH:19][CH2:18][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 109776384-Bromo-7-chloroquinolineHCID 178418416HCID 178418416, compound

Product 1

HCID 23298203(7-Chloroquinolin-4-yl)methanolYield 68%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
120 °C

Procedure

A 200 ml stainless steel autoclave was loaded with 4-bromo-7-chloroquinoline (1.2 g, 5.0 mmol) (Can. Pat. CA 94-2133620 941004), bis(triphenylphosphine)palladium chloride (0.1 g), triethylamine (3 ml) and ethanol (40 ml) and pressurized to 200 psi with carbon monoxide. The autoclave was heated at 120° C. for 12 hours, cooled, and vented. Solids were removed by filtration through celite and the mother liquor concentrated in vacuo. The residue was taken up in chloroform (50 ml), washed with water (3×50 ml), saturated brine (50 ml), and dried (Na2SO4). Filtration and removal of solvent left 1.3 g of a brown liquid. Flash chromatography on silica using 1 vol % CH3CN in CH2Cl2 as eluent afforded product as a colorless syrup which solidified to a waxy solid. This solid was dissolved in methanol (50 ml) and sodium borohydride was added over two hours until judged complete by TLC. The reaction was diluted with water and acidified with 1N hydrochloric acid and then neutralized with sodium bicarbonate. The resulting solid was recovered via filtration, dissolved in ethyl acetate and dried (MgSO4). Filtration and concentration afforded the desired compound (mp: 160° C., 0.66 g, 68% over two steps).

Workup

  1. temperaturecooled
  2. customSolids were removed by filtration through celite
  3. concentrationthe mother liquor concentrated in vacuo
  4. washwashed with water (3×50 ml), saturated brine (50 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationFiltration and removal of solvent
  7. waitleft 1.3 g of a brown liquid
  8. customFlash chromatography on silica using 1 vol % CH3CN in CH2Cl2 as eluent afforded product as a colorless syrup which
  9. filtrationThe resulting solid was recovered via filtration
  10. dissolutiondissolved in ethyl acetate
  11. dry with materialdried (MgSO4)
  12. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-55d0c6c173fd497e88c553422ec626a3
Source dataset
uspto-grants-2000_09
Patent number
US06117884

Reaction notes

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