3-Thiophenecarboxaldehyde → 3-((Thiophen-3-yl)oxomethyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene

HRID 1836915Notes

Reaction equation

HRID 1836915 reaction equation
O1CCOC1[C:6]1[C:15]([CH:16]([C:18]2[CH:22]=[CH:21][S:20][CH:19]=2)[OH:17])=[CH:14][C:13]2[C:12]([CH3:24])([CH3:23])[CH2:11][CH2:10][C:9]([CH3:26])([CH3:25])[C:8]=2[CH:7]=1.BrC1C(C2OCCO2)=CC2C(C)(C)CCC(C)(C)C=2C=1.S1C=CC(C=O)=C1.O1CCOC1C1C(C(C2SC=CC=2)O)=CC2C(C)(C)CCC(C)(C)C=2C=1>ClCCl>[S:20]1[CH:21]=[CH:22][C:18]([C:16](=[O:17])[C:15]2[CH:6]=[CH:7][C:8]3[C:9]([CH3:26])([CH3:25])[CH2:10][CH2:11][C:12]([CH3:23])([CH3:24])[C:13]=3[CH:14]=2)=[CH:19]1

Participants

6

Reactant 4

HCID 681353-ThiophenecarboxaldehydeHCID 234989352-(1,3-Dioxolan-2-yl)-3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthaleneHCID 234989602-(1,3-Dioxolan-2-yl)-3-[1-hydroxy-1-(thiophene-2-yl)methyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthaleneHCID 234989702-(1,3-Dioxolane-2-yl)-3-[(thiophen-3-yl)hydroxymethyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene

Product 1

HCID 865853933-((Thiophen-3-yl)oxomethyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthaleneYield 33.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(1,3-dioxolane-2-yl)-3-[(thiophen-3-yl)hydroxymethyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (1.31 g, 3.86 mmol) [prepared from 3-bromo-2-(1,3-dioxolane-2-yl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene and 3-thiophenecarboxaldehyde as previously described for the preparation of 2-(1,3-dioxolane-2-yl)-3-[(thiophene-2-yl)hydroxymethyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene] in 13 ml of anhydrous dichloromethane was cooled to 0° C. and Des-Martin periodinane (1.80 g, 4.25 mmol) was added over 3 minutes. The reaction was warmed to rt and stirred for 4 hours. The cloudy solution was diluted with 200 ml of dichloromethane and washed with sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. This residue was then dissolved in 10 ml of tetrahydrofuran and stirred vigorously while adding 10 ml of an aqueous 1N HCl solution. Mixture was stirred for two hours and partitioned between ethyl acetate and water. The resulting organic layer was washed with brine, dried over magnesium sulfate and dried in vacuo. Chromatographic separation was achieved using a silica gel column eluting with a gradient starting with 2% ethyl acetate/hexanes to 8% ethyl acetate/hexanes to give 2-formyl-[3-((thiophen-3-yl)oxomethyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (386 mg).

Workup

  1. additionDes-Martin periodinane (1.80 g, 4.25 mmol) was added over 3 minutes
  2. temperatureThe reaction was warmed to rt
  3. washwashed with sodium bicarbonate solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThis residue was then dissolved in 10 ml of tetrahydrofuran
  8. stirringstirred vigorously
  9. additionwhile adding 10 ml of an aqueous 1N HCl solution
  10. stirringMixture was stirred for two hours
  11. custompartitioned between ethyl acetate and water
  12. washThe resulting organic layer was washed with brine
  13. dry with materialdried over magnesium sulfate
  14. customdried in vacuo
  15. customChromatographic separation
  16. washeluting with

Sources & evidence

ORD record
ord-431d199918464c35bed3b6ec52ff48aa
Source dataset
uspto-grants-2004_08
Patent number
US06777418B2

Reaction notes

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