Hydrochloric Acid → 2-Methoxy-5-(nitromethylthio)thiophene

Temperature

-40 °C

A hexane/THF solution of lithium diisopropylamide was obtained by adding butyllithium (1.55 M hexane solution, 86.45 ml) to a stirred solution of diisopropylamine (101 g) in THF (100 ml) at -70° C. under an argon atmosphere. After 1 hour at -70° C., a solution of 2-(2-methoxythien-5-ylthio)acetic acid (obtained as described in West German OLS no. 1512272; 10.91 g) was added to the diisopropylamide solution during 20 minutes at -70° C. After 2 hours at this temperature, it was allowed to warm up to -40° C. Isoamyl nitrate (21.2 ml) was then added. The mixture was stirred at -40° C. for 2 hours and then at ambient temperature for 16 hours. The mixture was acidified to pH 2 with 2 M hydrochloric acid and stirred for 1 hour, during which time the intermediate 2-nitro-2-(2-methoxythien-5-ylthio)acetic acid underwent decarboxylation. The mixture was added to water (100 ml) and extracted with ethyl acetate. The combined organic layers were washed first with saturated sodium bicarbonate solution (200 ml) (to remove unreacted acidic starting material) and then with 2 M sodium hydroxide (2×200 ml). The latter washings were acidified to pH 2 with 2 M hydrochloric acid and extracted with ether (2×300 ml). The combined extracts were dried (MgSO4) in the presence of activated charcoal and evaporated. The residual oil was purified by column chromatography on silica (300 g) using 15% v/v ethyl acetate/hexane as eluant to give 2-methoxy-5-(nitromethylthio)thiophene (2.9 g) as an oil; NMR (90 MHz): 3.9 (s,3H), 5.25 (s,2H), 6.1 (d,1H), 7.0 (d,1H).

1. waitat ambient temperature for 16 hours
2. extractionextracted with ethyl acetate
3. washThe combined organic layers were washed first with saturated sodium bicarbonate solution (200 ml) (to remove unreacted acidic starting material)
4. extractionextracted with ether (2×300 ml)
5. dry with materialThe combined extracts were dried (MgSO4) in the presence of activated charcoal
6. customevaporated
7. customThe residual oil was purified by column chromatography on silica (300 g)

ORD record

ord-8cfe3ad2b3a248f5a9e6e53d2e5fb60b

Source dataset

uspto-grants-1992_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05102905