Hydrochloric Acid → Ethyl (4-bromo-2-methylphenyl)(oxo)acetate

To a suspension of NaBH4 (5.56 g, 147 mmol) in THF (100 mL) was added dropwise trifluoroacetic acid (16.7 g, 147 mmol) at a rate which maintained the reaction temperature between 25 and 35° C., and the resulting slurry was stirred at room temperature for 30 minutes. To the trifluoroacetoxyborohydride suspension was added a solution of ethyl (4-bromo-2-methylphenyl)-(methoxyimino)ethanoate (11.0 g, 36.7 mmol) in 20 mL of THF. The resulting light yellow mixture was stirred at reflux for 3.5 h and then at room temperature for 16 h. The excess NaBH4 was neutralized by the careful addition of conc. HCl (pH<3). The pH was adjusted to >9 with 50% aq. NaOH and the alkaline mixture was diluted with water (100 mL). The THF was evaporated and the aq. residue was extracted with CH2Cl2 (3×100 mL). The organic extracts were washed with brine, dried (Na2SO4), filtered, and the CH2Cl2 was removed in vacuo to give crude product as a yellow oil. The oil was dissolved in CH2Cl2 and anhydrous HCl was bubbled into the solution. The resulting HCl salt was collected by vacuum filtration and dried to give the desired product as a white solid (5.7 g, 58%). mp 211-214° C. (d); 1H NMR (DMSO-d6) δ 2.35 (s, 3H), 3.67 (d, 2H, J=6.0 Hz), 4.39 (m, 1H), ˜5.30 (bs, 1H), 7.45-7.48 (m, 2H), 7.56 (d, 1H, J=8.8 Hz), 8.66 (s, 3H).

1. temperaturemaintained the reaction temperature between 25 and 35° C.
2. stirringThe resulting light yellow mixture was stirred
3. temperatureat reflux for 3.5 h
4. waitat room temperature for 16 h
5. customThe THF was evaporated
6. extractionthe aq. residue was extracted with CH2Cl2 (3×100 mL)
7. washThe organic extracts were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customthe CH2Cl2 was removed in vacuo
11. customto give crude product as a yellow oil
12. customanhydrous HCl was bubbled into the solution
13. filtrationThe resulting HCl salt was collected by vacuum filtration
14. customdried

ORD record

ord-2a368083dafe433786cdf3418a8b283c

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06924298B2