反应详情

To a solution of 4-[4-(4-chlorophenoxy)phenylthiomethyl]tetrahydropyran-4-carboxylic acid (580 mg, 1.53 mmol) and N,N-dimethylformamide catalyst (22 μL) in methylene chloride (15 mL) at 0° C. was added oxalyl chloride (0.33 mL, 3.83 mmol) dropwise over 10 minutes. The mixture was warmed to room temperature over 1 hour, the partial slurry stirred an additional 12 hours, and concentrated in vacuo until the theoretical mass of the acid chloride was obtained. The residue was suspended intetrahydrofuran (7.5 mL), and methanol (0.19 mL, 4.59 mmol), followed by triethylamine (0.64 mL, 4.59 mmol) was added. The mixture was heated to reflux for 14 hours, concentrated, and the resulting residue partitioned between methylene chloride (150 mL) and 1M aqueous hydrochloric acid (50 mL). The aqueous layer was back extracted with additional portions of methylene chloride (2×30 mL), the combined extracts dried over magnesium sulfate, and concentrated to afford crude 4-[4-(4-chlorophenoxy)phenylthiomethyl]-tetrahydropyran-4-carboxylic acid methyl ester, which was taken directly into the next reaction without further purification. 1HNMR (CDCl3) δ 1.62. (m, 2H), 2.15 (dm, J=13.6 Hz, 2H), 3.13 (s, 2H), 3.47 (td, J=11.9, 2.4 Hz, 2H), 3.59 (s, 3H), 3.81 (dt, J=12.0, 4.1 Hz, 2H), 6.92 (d, J=8.9 Hz, 2H), 7.29 (d, J=8.8 Hz, 2H), 7.36 (d, J=8.8 Hz, 2H).

1. concentrationconcentrated in vacuo until the theoretical mass of the acid chloride
2. customwas obtained
3. additionwas added
4. temperatureThe mixture was heated
5. temperatureto reflux for 14 hours
6. concentrationconcentrated
7. customthe resulting residue partitioned between methylene chloride (150 mL) and 1M aqueous hydrochloric acid (50 mL)
8. extractionThe aqueous layer was back extracted with additional portions of methylene chloride (2×30 mL)
9. dry with materialthe combined extracts dried over magnesium sulfate
10. concentrationconcentrated