4-Methoxy-alpha-toluenethiol → Ethyl 2-fluoro-3-((4-methoxybenzyl)thio)benzoate

Temperature

90 °C

1,4-dioxane (250 mL) was degassed by purging with N2 gas for 30 min and to this, were added a solution of compound A2 (13.2 g, 53.4 mmol) in 1,4-dioxane (50 mL; degassed), (4-methoxyphenyl)methanethiol (PMBSH) (8.2 g, 53.4 mmol), xantphos (1.54 g, 2.66 mmol), diisopropyl ethyl amine (19.6 mL, 106.8 mmol) and Pd2(dba)3 (1.22 g, 1.33 mmol) at RT. The reaction mixture was heated to 90° C. and stirred for 2 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with hexane (450 mL) and stirred at RT for 15 min. The resultant solution was filtered through celite and washed with hexane (100 mL). The filtrate was washed water (250 mL) dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified through silica gel column chromatography using 3-4% EtOAc/Hexanes to afford compound A3 (15 g, 88%) as pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.78-7.74 (m, 1H), 7.43-7.39 (m, 1H), 7.19 (d, J=8.0 Hz, 2H), 7.07-7.04 (m, 1H), 6.80 (d, J=8.0 Hz, 2H), 4.41 (q, J=7.2 Hz, 2H), 4.08 (s, 2H), 3.78 (s, 3H), 1.41 (t, J=7.2 Hz, 3H). LC-MS (ESI): 89.7%; m/z 318.9 (M−H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.22 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

1. custom1,4-dioxane (250 mL) was degassed
2. customby purging with N2 gas for 30 min
3. customafter completion of the reaction
4. stirringstirred at RT for 15 min
5. filtrationThe resultant solution was filtered through celite
6. washwashed with hexane (100 mL)
7. washThe filtrate was washed water (250 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto obtain the crude
12. customThe crude was purified through silica gel column chromatography

ORD record

ord-52e2b35c40ee411da63c4136ecea87ad

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051320B1