Tin tetrachloride → (2-Benzyl-4,5-dimethyl-thiophen-3-yl)-(4-methoxy-3,5-dimethyl-phenyl)-methanone

Temperature

-78 °C

To a suspension of 3,5-dimethyl-p-anisic acid (15.2 g, 84.4 mmol, RN-21553-46-8) in anhydrous methylene chloride (200 mL) at room temperature under nitrogen was added oxalyl chloride (9.6 mL, 110 mmol) and N,N-dimethylformamide (5 drops). After two hours the solvent was removed. The resulting residue was dissolved in anhydrous methylene chloride (200 mL), and added to 2,3-dimethyl-5-benzylthiophene (17.1 g, 84.4 mmol) under nitrogen. The resulting mixture was, cooled to −78° C., and tin(IV) chloride (10.8 mL, 92.8 mmol) was added quickly. The −78° C. bath was removed and the mixture was stirred at room temperature for 2 h. The reaction mixture was then poured onto ice water (1 L), and the resulting mixture was extracted once with diethyl ether (700 mL), and a second time with diethyl ether (400 mL). The combined diethyl ether extracts were washed with ice water (500 mL), dilute sodium bicarbonate (500 mL), water (500 mL), brine (1 L), and then dried (Na2SO4). Concentration under reduced pressure gave the title compound as a yellow oil (25.2 g, 82%): NMR (DMSO-d6): δ7.40 (s, 2H), 7.24-7.15 (m, 3H), 7.06 (d, 2H), 3.83 (s, 2H), 3.70 (s, 3H), 2.28 (s, 3H), 2.26 (s, 6H), 1.83 (s, 3H).

1. customAfter two hours the solvent was removed
2. dissolutionThe resulting residue was dissolved in anhydrous methylene chloride (200 mL)
3. customThe −78° C. bath was removed
4. additionThe reaction mixture was then poured onto ice water (1 L)
5. extractionthe resulting mixture was extracted once with diethyl ether (700 mL)
6. washThe combined diethyl ether extracts were washed with ice water (500 mL), dilute sodium bicarbonate (500 mL), water (500 mL), brine (1 L)
7. dry with materialdried (Na2SO4)
8. concentrationConcentration under reduced pressure

ORD record

ord-3e8481887e004ee5b059af161777105f

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06251936B1