2-Pyridinecarboxaldehyde → HCID 15204724, compound

HRID 1769059Notes

Reaction equation

HRID 1769059 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH2:8][OH:9])(C)C.C([Li])CCC.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]=[O:25].[Cl-].[NH4+]>CCOCC.CCCCCC.C(OCC)(=O)C>[OH:9][CH2:8][C:7]1[CH:10]=[CH:11][CH:12]=[C:5]([O:4][CH3:1])[C:6]=1[CH:24]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=1)[OH:25]

Participants

8

Reactant 4

HCID 142732-PyridinecarboxaldehydeHCID 25517Ammonium ChlorideHCID 2759474(3-Isopropoxyphenyl)methanolHCID 178418339Butyllithium

Product 1

HCID 15204724HCID 15204724, compoundYield 25.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

To a mixture of 30 g (0.18 mol) of 3-isopropoxybenzyl alcohol in 600 ml of ether cooled to -20° C. was added in portions 38.7 ml (0.387 mol) of n-butyllithium (10M) in hexane over a 20 min period, and the reaction mixture was allowed to warm to room temperature and stirred for 2 hr. The above reaction mixture was cooled to -20° C., 23.1 g (0.216 mol) of pyridine-2-carboxaldehyde was added in one portion to the mixture, and the resulting reaction mixture was allowed to warm to room temperature and stirred for 1 hr. Ammonium chloride solution (200 ml) and 100 ml of ethyl acetate were added to the mixture. The resulting mixture was separated, the aqueous layer was extracted with methylene chloride (2×200 ml), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated. The diol was purified by chromatography on silica gel eluting with ethyl acetate/hexane (9:1; and 0.05 % TEA). The solvent was concentrated in vacuo, the brown oil was dissolved in methylene chloride/hexane, and removal of methylene chloride in vacuo to 1/2 of its volume afforded 11.1 g (22.6%) of 2-[1-hydroxy-(6'-hydroxymethyl-2'-isopropoxy) -benzyl]pyridine (Formula XIII: R1 =R7 =H; R2 =2'--OCH (CH3)2), as a tan solid.

Workup

  1. temperatureto warm to room temperature
  2. customThe above reaction mixture
  3. temperaturewas cooled to -20° C.
  4. customthe resulting reaction mixture
  5. temperatureto warm to room temperature
  6. stirringstirred for 1 hr
  7. customThe resulting mixture was separated
  8. extractionthe aqueous layer was extracted with methylene chloride (2×200 ml)
  9. washthe combined organic layer was washed with brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. customThe diol was purified by chromatography on silica gel eluting with ethyl acetate/hexane (9:1; and 0.05 % TEA)
  13. concentrationThe solvent was concentrated in vacuo
  14. dissolutionthe brown oil was dissolved in methylene chloride/hexane
  15. customremoval of methylene chloride in vacuo to 1/2 of its volume

Sources & evidence

ORD record
ord-52cfb8d5ce0a4b76921e966ceb85e98a
Source dataset
uspto-grants-1995_01
Patent number
US05380729

Reaction notes

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