N,N,N',N'-Tetramethylethylenediamine → HCID 58561772, compound

To a solution of TMEDA (1.95 mL, 12.9 mmol) in anhydrous THF (8 mL) was slowly added a solution of sec-BuLi (1.4 M solution in cyclohexane, 18.5 mL, 25.8 mmol) at −78° C., followed by a solution of 4-fluoro-2-methoxy-benzoic acid (44, 1.0 g, 5.88 mmol) in anhydrous THF (2 mL) at −78° C. under an atmosphere of N2. The mixture stirred at −78° C. for 2 h before a solution of dimethyl disulfide (2.1 mL, 23.5 mmol) in anhydrous THF (2 mL) was added slowly. The mixture was stirred at same temperature for 1 h before it was warmed up to room temperature and quenched with H2O. The crude mixture was diluted with H2O (10 mL) and extracted with EtOAc (10 mL). Aqueous layer was collected and acidified with 2 M HCl, followed by extraction by EtOAc (2×20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (Isco CombiFlash Companion unit, 40 g Redisep column, 20% to 50% EtOAc/hexane) to give 4-fluoro-2-methoxy-6-(methylthio) benzoic acid as a white solid (46, 0.22 g, 17%): 1H NMR (300 MHz, CDCl3) δ 8.07 (dd, J=15.3, 4.5 Hz, 1H), 7.03 (t, J=8.7 Hz, 1H), 4.11 (s, 3H), 2.49 (s, 1H); MS (ESI+) m/z 217 (M+H).

1. additionwas added slowly
2. customquenched with H2O
3. additionThe crude mixture was diluted with H2O (10 mL)
4. extractionextracted with EtOAc (10 mL)
5. customAqueous layer was collected
6. extractionfollowed by extraction by EtOAc (2×20 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was chromatographed over silica gel (Isco CombiFlash Companion unit, 40 g Redisep column, 20% to 50% EtOAc/hexane)

ORD record

ord-86d8f126eb3c40af91bce52316543627

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045445B2