2-Thiophenecarboxaldehyde → 2-(1,3-Dioxolan-2-yl)-3-[1-hydroxy-1-(thiophene-2-yl)methyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene

HRID 1836888Notes

Reaction equation

HRID 1836888 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:15](Br)=[CH:14][C:13]2[C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10][C:9]([CH3:20])([CH3:19])[C:8]=2[CH:7]=1.[Li]CCCC.[S:26]1[CH:30]=[CH:29][CH:28]=[C:27]1[CH:31]=[O:32].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:15]([CH:31]([OH:32])[C:27]2[S:26][CH:30]=[CH:29][CH:28]=2)=[CH:14][C:13]2[C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10][C:9]([CH3:20])([CH3:19])[C:8]=2[CH:7]=1

Participants

7

Reactant 4

HCID 73642-ThiophenecarboxaldehydeHCID 25517Ammonium ChlorideHCID 234989352-(1,3-Dioxolan-2-yl)-3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthaleneHCID 178418339Butyllithium

Product 1

HCID 234989602-(1,3-Dioxolan-2-yl)-3-[1-hydroxy-1-(thiophene-2-yl)methyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. tetrahydrofuran (3.0 mL) solution of 2-(1,3-dioxolan-2-yl)-3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (253 mg, 0.75 mmol) was added n-BuLi (1.6 M in hexane, 0.49 mL). The reaction mixture gradually thickened over 45 min. A solution of thiophene-2-carboxaldehyde (0.09 mL, 0.94 mmol) in tetrahydrofuran (0.75 mL) was added dropwise to the above slurry. The reaction mixture rapidly became homogeneous and was stirred at −78° C. for 45 minutes. Saturated ammonium chloride and ethyl acetate were added and the layers were separated. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give a yellow oil which was purified by preparative thin layer chromatography (15% ethyl acetate/hexane) to give 2-(1,3-dioxolan-2-yl)-3-[1-hydroxy-1-(thiophene-2-yl)methyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene as a waxy solid (190 mg, 67%).

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customto give a yellow oil which
  6. customwas purified by preparative thin layer chromatography (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5baef5b61d314b15a5261747a294b0fb
Source dataset
uspto-grants-2004_08
Patent number
US06777418B2

Reaction notes

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