N,N-Dimethylthioformamide → 2-(5-fluoro-2-methoxyphenyl)-2-hydroxy-N,N-dimethylethanethioamide

Temperature

-78 °C

To a solution of lithium diisopropylamide, 2M in THF/n-heptane (210 mL, 583 mmol) was added THF (100 mL) and the solution cooled to −78° C. under nitrogen. This was then added dropwise over 1 h to a solution of the 5-fluoro-2-methoxybenzaldehyde (50 g, 0.32 mmol) and N,N-dimethylthioformamide (34.7 g, 389 mmol) in dry THF (200 mL). This was warmed to −5° C. and quenched with water (400 mL). The solution was filtered and washed with diethyl ether, the aqueous layer was extracted with ether (1 L). The combined organic layers were washed with water (500 mL), dried (MgSO4) and the solvent removed in vacuo to give a crystalline suspension in oil. This was triturated in ether and filtered to give a crystalline solid (21.8 g, 28%); δH (300 MHz, CDCl3) 7.16–6.81 (3H, m, ArH), 5.81–5.75 (1H, m, CHOH), 5.31–5.22 (1H, m, OH), 4.89 (3H, s, OCH3), 3.50 (3H, s, N(CH3)2) and 3.08 (3H, s, N(CH3)2).

1. temperatureThis was warmed to −5° C.
2. customquenched with water (400 mL)
3. filtrationThe solution was filtered
4. washwashed with diethyl ether
5. extractionthe aqueous layer was extracted with ether (1 L)
6. washThe combined organic layers were washed with water (500 mL)
7. dry with materialdried (MgSO4)
8. customthe solvent removed in vacuo
9. customto give a crystalline suspension in oil
10. customThis was triturated in ether
11. filtrationfiltered

ORD record

ord-820eadeee1354a24aee9305df1d80a23

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07037932B2