Hydrochloric Acid → 2-(2-Bromo-5-chlorophenyl)-4,4-dimethyl-4,5-dihydrooxazole

To a suspension of 2-bromo-5-chlorobenzoic acid (1.5 g, 6.4 mmol) in methylene chloride (15 mL) at room temperature was added oxalyl chloride (969 mg, 666 μL, 7.64 mmol) and 2 drops of dimethylformamide; bubbling commenced and the mixture ultimately became homogenous. The mixture was stirred at roorm temperature for 7 hours and concentrated. The resulting acid chloride residue was dissolved in methylene chloride (15 mL). Triethylamine (325 mg, 450 μL, 3.2 mmol) was added, followed by 2-amino-2-methyl-1-propanol (627 mg, 672 μL, 7.04 mmol) and the reaction was allowed to stir at rt 3 h. The mixture was poured into 1 N hydrochloric acid (50 mL), extracted with methylene chloride (2×75 mL). The combined extracts were washed with saturated aqueous sodium bicarbonate, brine and dried over magnesium sulfate, filtered and concentrated and dried in vacuo. The crude amide residue was dissolved in methylene chloride (15 mL) and thionyl chloride (1.29 g, 794 μL, 10.9 mmol) was added. Stirring at room temperature was carried out for 4 h after which the mixture was poured into saturated sodium bicarbonate (50 mL). The pH was adjusted to 9 by the addition of solid sodium bicarbonate and further basified by the addition of several milliliters of aqueous sodium hydroxide (5 N). The biphasic mixture was extracted with methylene chloride (150+50 mL). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated to afford the crude residue which was purified by silica gel chromatography (80% hexanes/20% ethyl acetate gradient) to yield 2-(2-bromo-5-chloro-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole (1.15 g, 62%).

1. custombubbling
2. concentrationconcentrated
3. dissolutionThe resulting acid chloride residue was dissolved in methylene chloride (15 mL)
4. stirringto stir at rt 3 h
5. extractionextracted with methylene chloride (2×75 mL)
6. washThe combined extracts were washed with saturated aqueous sodium bicarbonate, brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customdried in vacuo
11. dissolutionThe crude amide residue was dissolved in methylene chloride (15 mL)
12. stirringStirring at room temperature
13. waitwas carried out for 4 h
14. extractionThe biphasic mixture was extracted with methylene chloride (150+50 mL)
15. washThe combined extracts were washed with brine
16. dry with materialdried over magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated
19. customto afford the crude residue which
20. customwas purified by silica gel chromatography (80% hexanes/20% ethyl acetate gradient)

ORD-Eintrag

ord-0cf243a3644b4598bdc7e7b8d6a97a96

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08653096B2