Sodium Azide → Ethyl (3R)-2-azido-4,4,4-trifluoro-3-methylbutanoate

48.5 g of crude ethyl (3S)-2-bromo-4,4,4-trifluoro-3-methylbutanoate (diastereomer mixture) were dissolved in 130 ml of DMF, and 17.98 g (276.55 mmol) of sodium azide were added at RT. The reaction mixture was stirred vigorously at RT overnight. The mixture was then diluted with 600 ml of ethyl acetate and washed with a 1:1 mixture, adjusted to pH 8, of sat. sodium chloride solution and water. After phase separation, the aqueous phase was re-extracted with 200 ml of ethyl acetate. The combined organic phases were washed successively twice with in each case 100 ml and twice with in each case 50 ml of a 1:1 mixture of sat. sodium chloride solution and water, dried over sodium sulphate and concentrated under reduced pressure without heating. The residue was briefly dried under high vacuum (careful when venting). This gave 32.8 g of ethyl (3R)-2-azido-4,4,4-trifluoro-3-methylbutanoate (diastereomer mixture) as a crude product which was directly reacted further.

1. washwashed with a 1:1 mixture
2. customAfter phase separation
3. extractionthe aqueous phase was re-extracted with 200 ml of ethyl acetate
4. washThe combined organic phases were washed successively twice with in each case 100 ml and twice with in each case 50 ml of a 1:1 mixture of sat. sodium chloride solution and water
5. dry with materialdried over sodium sulphate
6. concentrationconcentrated under reduced pressure
7. temperaturewithout heating
8. customThe residue was briefly dried under high vacuum (careful when venting)
9. customThis gave 32.8 g of ethyl (3R)-2-azido-4,4,4-trifluoro-3-methylbutanoate (diastereomer mixture) as a crude product which was directly reacted further

ORD record

ord-c510a20991b742ff9fb62c83039e409b

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309198B2