2-Methylthiophene → 1-(5-Methyl-thien-2-yl)3,4-dihydro-4,4-dimethyl-7-bromo-naphthalene

Temperature

0 °C

To a cold (−78° C.) solution of 2-methylthiophene (800 mg, 8.1 mmol) in THF (10 mL) was added n-BuLi (1.6M solution in hexane, 5 mL). The mixture was stirred for 1.5 hours and transferred to a cold (−78° C.) flask containing 3,4-dihydro-4,4-dimethyl-7-bromo-1(2H)-naphthalenone (Compound A, 1.63 g, 6.5 mmol), in THF (15 mL). The mixture was gradually warmed to 0° C. The reaction mixture was diluted with ether:ethylacetate (1:1, 80 mL), washed with water (10 mL), brine (10 mL), dried with MgSO4 and the solvent was removed by evaporation. The crude material was dissolved in dichloroethane (20 mL) and pTSA (40 mg) was added. The mixture was stirred at ambient temperature for 16 hours and at 50° C. for 4 hours. The reaction mixture was diluted with ether (150 mL), washed with aqueous 10% NaHCO3 (10 mL), brine (10 mL) and dried with MgSO4. Purification by chromatography on silica gel gave 1.35 g of the title compound as a white solid.

1. customtransferred to a cold (−78° C.) flask
2. washwashed with water (10 mL), brine (10 mL)
3. dry with materialdried with MgSO4
4. customthe solvent was removed by evaporation
5. dissolutionThe crude material was dissolved in dichloroethane (20 mL)
6. additionpTSA (40 mg) was added
7. stirringThe mixture was stirred at ambient temperature for 16 hours and at 50° C. for 4 hours
8. additionThe reaction mixture was diluted with ether (150 mL)
9. washwashed with aqueous 10% NaHCO3 (10 mL), brine (10 mL)
10. dry with materialdried with MgSO4
11. customPurification by chromatography on silica gel

ORD record

ord-db1baf09c31e4b26bae399fd6806fe09

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06538149B1