Oxalyl chloride → 7-Methylchroman-4-one

A stirred solution of 5.0 grams (0.028 mole) of 3-(3-methylphenoxy)propanoic acid (i) and 5.3 grams (0.042 mole) of oxalyl chloride in 100 mL of methylene chloride was cooled to −5° C. and a few drops of DMF was added. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for about two hours. After this time, the reaction mixture was concentrated under reduced pressure to a residue: which was 3-(3-methylphenoxy)propanoic acid chloride. The acid chloride was stored under a nitrogen atmosphere for about 18 hours, and then it was dissolved in 50 mL of methylene chloride. The stirred solution was cooled to −4° C. and 4.1 grams (0.031 mole) of aluminum chloride was added portionwise while maintaining the reaction mixture temperature at 5° C. or less. Upon completion of addition, the reaction mixture was maintained at 5° C. for about three hours. After this time, the reaction mixture was poured into ice and extracted with three 100 mL portions of methylene chloride. The combined extracts were washed with two 50 mL portions of water and dried with sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel using mixtures of ethyl acetate and hexane as an eluant. The appropriate fractions of eluate were combined and concentrated under reduced pressure, yielding 3.5 grams of subject compound. The NMR spectrum was consistent with the proposed structure.

1. additionUpon completion of addition
2. concentrationAfter this time, the reaction mixture was concentrated under reduced pressure to a residue
3. waitThe acid chloride was stored under a nitrogen atmosphere for about 18 hours
4. dissolutionit was dissolved in 50 mL of methylene chloride
5. temperatureThe stirred solution was cooled to −4° C.
6. temperaturewhile maintaining the reaction mixture temperature at 5° C. or less
7. additionUpon completion of addition
8. temperaturethe reaction mixture was maintained at 5° C. for about three hours
9. additionAfter this time, the reaction mixture was poured into ice
10. extractionextracted with three 100 mL portions of methylene chloride
11. washThe combined extracts were washed with two 50 mL portions of water
12. dry with materialdried with sodium sulfate
13. filtrationThe mixture was filtered
14. concentrationthe filtrate was concentrated under reduced pressure to a residue
15. customThe residue was purified by column chromatography on silica gel using mixtures of ethyl acetate and hexane as an eluant
16. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-a60bdbcd27654cb58fc5c317452e6d42

Quelldatensatz

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07417057B2