Triethylamine → 3-(3,4-dihydro-2H-thiopyran-5-yl)benzyl alcohol

HRID 2254473Notes

Reaction equation

HRID 2254473 reaction equation
C[O:2][CH:3]([O:11]C)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6](Br)[CH:5]=1.[S:13]1[CH2:18][CH2:17][CH2:16][C:15](=O)[CH2:14]1.CS(Cl)(=O)=O.C(N(CC)CC)C>C(OCC)(=O)C>[S:13]1[CH:14]=[C:15]([C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[CH2:3][OH:11])[CH2:16][CH2:17][CH2:18]1.[S:13]1[CH2:18][CH2:17][CH:16]=[C:15]([C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[CH2:3][OH:2])[CH2:14]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1053951-Bromo-3-(dimethoxymethyl)benzeneHCID 140474Dihydro-2H-thiopyran-3(4H)-one

Product 2

HCID 536854473-(5,6-dihydro-2H-thiopyran-3-yl)benzyl alcoholYield 1%HCID 539611723-(3,4-dihydro-2H-thiopyran-5-yl)benzyl alcoholYield 2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

534 mg of 3-(tetrahydro-3-hydroxy-3-thiopyranyl)benzaldehyde dimethyl acetal obtained by performing the same reaction as in Referential Example 35 using 3-bromobenzaldehyde dimethyl acetal and tetrahydrothiopyran-3-one as starting materials was dissolved in 5 ml of ethyl acetate, and with stirring under ice cooling, 187 microliters of methanesulfonyl chloride and 553 microliters of triethylamine were added. The mixture was stirred for 30 minutes. The triethylamine hydrochloride was separated by filtration and the solvent was evaporated. The residue was dissolved in 20 ml of benzene, and 373 mg of 90% potassium tert-butoxide was added, and the mixture was stirred at room temperature for 15 hours. Ethyl ether and water were added to the reaction mixture, and the mixture was worked up in a customary manner. The resulting 3-dihydrothiopyranylbenzaldehyde dimethyl acetal was dissolved in a mixture of 3 ml of 1 N HCl and 6 ml of tetrahydrofuran. The solution was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was distributed between ethyl ether and water, and worked up in a customary manner. The resulting formyl compound was dissolved in 20 ml of tetrahydrofuran, and 380 mg of lithium aluminium hydride was added. The mixture was stirred for one hour under ice cooling. The reaction mixture was poured into ice water, worked up in a customary manner and purified by silica gel column chromatography [Wakogel C-200, 20 g; eluting solvent: hexane/ethyl acetate=2/1] to give 7 mg (yield 2%) of the captioned 3-(3,4-dihydro-2H-thiopyran-5-yl)benzyl alcohol and 4 mg (yield 1%) of 3-(5,6-dihydro-2H-thiopyran-3-yl)benzyl alcohol.

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. customThe triethylamine hydrochloride was separated by filtration
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in 20 ml of benzene
  5. addition373 mg of 90% potassium tert-butoxide was added
  6. stirringthe mixture was stirred at room temperature for 15 hours
  7. additionEthyl ether and water were added to the reaction mixture
  8. dissolutionThe resulting 3-dihydrothiopyranylbenzaldehyde dimethyl acetal was dissolved in a mixture of 3 ml of 1 N HCl and 6 ml of tetrahydrofuran
  9. stirringThe solution was stirred at room temperature for 3 hours
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. dissolutionThe resulting formyl compound was dissolved in 20 ml of tetrahydrofuran
  12. addition380 mg of lithium aluminium hydride was added
  13. stirringThe mixture was stirred for one hour under ice cooling
  14. additionThe reaction mixture was poured into ice water
  15. custompurified by silica gel column chromatography [Wakogel C-200, 20 g; eluting solvent: hexane/ethyl acetate=2/1]

Sources & evidence

ORD record
ord-15b02fbbe9834b9fb499c73501c06ae3
Source dataset
uspto-grants-1993_08
Patent number
US05234946

Reaction notes

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