Trifluoroacetic acid → HCID 9815473, compound

Temperature

0 °C

n-Butyllithium (1.6 M in hexane, 20.16 ml) was added to a stirred solution of diisopropylamine (4.52 ml) in tetrahydrofuran (60 ml) at −78° C. After 15 min, ethyl isovalerate (4.03 ml) was added and the reaction left for 1 h, before tert-butyl bromoacetate (4.78 ml) was added and the reaction allowed to warm to 0° C. After 12 h water (10 ml) was added and the solvent removed in vacuo. The resulting slurry was extracted with ethyl acetate (3×20 ml), and the combined organic extracts washed with water (2×50 ml), brine (50 ml), dried over magnesium sulphate (2 g), and the solvent removed in vacuo to yield a brown oil. The oil was dissolved in dichloromethane (60 ml) and trifluoroacetic acid (12 ml) was added and the reaction stirred for 12 h. The reaction was evaporated in vacuo and the residue azeotroped with heptane to dryness. The residue was dissolved in aqueous sodium hydroxide (2M, 40 ml) and washed with dichloromethane (2×10 ml), the aqueous layer acidified with hydrochloric acid (2M) and extracted with ethyl acetate (3×10 ml). The combined ethyl acetate extracts were washed with water (10 ml) and brine (10 ml), dried over magnesium sulphate (2 g) and evaporated to give the title compound as a brown oil (4.5 g).

1. additionwas added
2. customthe solvent removed in vacuo
3. extractionThe resulting slurry was extracted with ethyl acetate (3×20 ml)
4. washthe combined organic extracts washed with water (2×50 ml), brine (50 ml)
5. dry with materialdried over magnesium sulphate (2 g)
6. customthe solvent removed in vacuo
7. customto yield a brown oil
8. customThe reaction was evaporated in vacuo
9. customthe residue azeotroped with heptane to dryness
10. dissolutionThe residue was dissolved in aqueous sodium hydroxide (2M, 40 ml)
11. washwashed with dichloromethane (2×10 ml)
12. extractionextracted with ethyl acetate (3×10 ml)
13. washThe combined ethyl acetate extracts were washed with water (10 ml) and brine (10 ml)
14. dry with materialdried over magnesium sulphate (2 g)
15. customevaporated

ORD record

ord-0d58a28258df426293369bc74bfc548e

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06462042B1