Methanol → HCID 18630056, compound

Temperature

100 °C

The 2-chloro-4-bromo-6-trimethylsilylbenzoic acid was diluted with thionyl chloride (3 mL, 41.1 mmol) and warmed. When gas evolution ceased, the solution was concentrated and stripped from toluene (2×) under vacuum to remove the excess thionyl chloride. The remaining dark oil was dissolved in toluene (12 mL), then the compound from example k (2.2 g, 19.5 mmol) was added and the mixture was heated at 100° C. until the reaction was complete by GLC. The resulting mixture was cooled to 0° C., and Et3N (1.32 g, 13.0 mmol) was added in a single portion, followed by the dropwise addition of methanol (0.62 g, 19.4 mmol) in toluene (1 mL). The reaction was warmed to RT and monitored to completion by GLC, then was diluted with ether and extracted with sat aq NaHCO3, dried (MgSO4), concentrated, and the residue dissolved in hexanes. The hexane solution was cooled to -78° C. and filtered to remove insoluble impurities, then the filtrate was concentrated and purified by RC with 1:49 EtOAc/hexanes to give 820 mg of N-ethyl-N-(1-methoxy-2,2-dimethylpropyl) 2-chloro-4-bromo-6-(trimethylsilyl)benzamide as a yellow oil.

1. temperaturewarmed
2. concentrationthe solution was concentrated
3. customto remove the excess thionyl chloride
4. dissolutionThe remaining dark oil was dissolved in toluene (12 mL)
5. temperatureThe resulting mixture was cooled to 0° C.
6. temperatureThe reaction was warmed to RT
7. extractionextracted with sat aq NaHCO3
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. dissolutionthe residue dissolved in hexanes
11. temperatureThe hexane solution was cooled to -78° C.
12. filtrationfiltered
13. customto remove insoluble impurities
14. concentrationthe filtrate was concentrated
15. custompurified by RC with 1:49 EtOAc/hexanes

ORD record

ord-55988b71148b4eb1a0d2bc8a27f9e45a

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05811411