3-Pyridinecarboxaldehyde → Tetrahydropyranyl ether

HRID 569152Notes

Reaction equation

HRID 569152 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1.Br[C:15]1[CH:20]=[CH:19][C:18](/[CH:21]=[C:22](\[CH3:28])/[CH2:23][O:24][CH2:25][CH2:26][OH:27])=[CH:17][CH:16]=1.CCCCCC.C([Li])CCC.[CH:40]1[CH:45]=[N:44][CH:43]=[C:42]([CH:46]=[O:47])[CH:41]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1.[N:44]1[CH:45]=[CH:40][CH:41]=[C:42]([CH:46]([OH:47])[C:15]2[CH:20]=[CH:19][C:18](/[CH:21]=[C:22](\[CH3:28])/[CH2:23][O:24][CH2:25][CH2:26][OH:27])=[CH:17][CH:16]=2)[CH:43]=1

Participants

9

Reactant 5

HCID 103713-PyridinecarboxaldehydeHCID 25517Ammonium ChlorideHCID 263182Tetrahydropyranyl etherHCID 20148641HCID 20148641, compoundHCID 178418244HCID 178418244, compound

Product 2

HCID 263182Tetrahydropyranyl etherHCID 20148659HCID 20148659, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

In 10 ml of anhydrous tetrahydrofuran was dissolved 910 mg of tetrahydropyranyl ether of 2-[(E)-3-(4-bromophenyl)-2-methylallyloxy]ethanol, and 1.9 ml of 1.5M n-butyl lithium hexane solution was dropped into the resulting solution at a temperature of -70° C. to -65° C., after which the resulting mixture was subjected to reaction at the same temperature for one hour. To the reaction mixture was dropwise added 1 ml of anhydrous tetrahydrofuran containing 0.27 ml of nicotinic aldehyde at a temperature of -70° C. to -65° C., and the resulting mixture was subjected to reaction at the same temperature for one hour. Subsequently, the solvent was removed by distillation under reduced pressure, and to the residue thus obtained were added 50 ml of ethyl acetate and 20 ml of a saturated aqueous ammonium chloride solution, after which the organic layer was separated, washed successively with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure. The residue thus obtained was purified by a column chromatography [Wako Silica Gel C-200, eluant: toluene:ethyl acetate (1:3 by volume)] to obtain 230 mg (yield 23.4%) of colorless, oily tetrahydropyranyl ether of 2-[(E)-3-[4-(pyridin-3-yl-hydroxymethyl)phenyl]-2-methylallyloxy]ethanol.

Workup

  1. additionwas dropped into the resulting solution at a temperature of -70° C. to -65° C.
  2. customafter which the resulting mixture was subjected to reaction at the same temperature for one hour
  3. customat a temperature of -70° C. to -65° C.
  4. customthe resulting mixture was subjected to reaction at the same temperature for one hour
  5. customSubsequently, the solvent was removed by distillation under reduced pressure
  6. customto the residue thus obtained
  7. customafter which the organic layer was separated
  8. washwashed successively with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was then removed by distillation under reduced pressure
  11. customThe residue thus obtained
  12. customwas purified by a column chromatography [Wako Silica Gel C-200, eluant: toluene:ethyl acetate (1:3 by volume)]

Sources & evidence

ORD record
ord-beb4ac9c5070456b85924c3ef789461e
Source dataset
uspto-grants-1988_03
Patent number
US04731370

Reaction notes

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