Hydrochloric Acid → Methyl 4-chloro-2,2-dimethylbutanoate

Temperature

-70 °C

The reaction vessel was dried and, under an argon atmosphere, 75.9 grams (0.75 mole) of diisopropylamine and 450 ml of tetrahydrofuran was added. The stirred solution was cooled to -70° C. and 48.0 grams (0.75 mole-484 ml of 1.5 molar in hexane) of n-butyl lithium was added. Upon completion of addition the reaction mixture stirred for 20 minutes and, at -70° C., 68.9 grams (0.675 mole) of methyl isobutyrate was added dropwise. Upon completion of addition the reaction mixture stirred for an additional 20 minutes and, at -70° C., 108.0 grams (0.75 mole) of 1-bromo-2-chloroethane was added dropwise. The reaction mixture was allowed to warm to ambient temperature where it stirred for 16 hours. After this time 500 ml of water, then 85 ml of concentrated hydrochloric acid, were added dropwise to the reaction mixture. Upon completion of addition the reaction mixture stirred for an additional five minutes. The organic layer was separated and washed with 150 ml of aqueous 10% hydrochloric acid. The combined aqueous layers were washed with 150 ml of methylene chloride. The combined organic layers were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was distilled under reduced pressure to give 84.2 grams of methyl 4-chloro-2,2-dimethylbutanoate; b.p. 80°-84° C./15 mm.

1. customThe reaction vessel was dried and, under an argon atmosphere
2. additionUpon completion of addition the reaction mixture
3. additionUpon completion of addition the reaction mixture
4. stirringstirred for an additional 20 minutes and, at -70° C.
5. temperatureto warm to ambient temperature where it
6. stirringstirred for 16 hours
7. additionUpon completion of addition the reaction mixture
8. stirringstirred for an additional five minutes
9. customThe organic layer was separated
10. washwashed with 150 ml of aqueous 10% hydrochloric acid
11. washThe combined aqueous layers were washed with 150 ml of methylene chloride
12. dry with materialThe combined organic layers were dried with magnesium sulfate
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under reduced pressure to a residual oil
15. distillationThe oil was distilled under reduced pressure

ORD record

ord-63b950c3bd774e1fa5aeae22e58894d1

Source dataset

uspto-grants-1985_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04552585