Ethyl chloroformate → HCID 11075646, compound

Temperature

23 °C

To an ice-cooled solution of (S)-2-(tert-butoxycarbonylamino)-4,4,4-trifluorobutanoic acid (1.0 g, 3.89 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.813 mL, 4.67 mmol) in THF (15 mL) was added dropwise ethyl chloroformate (0.409 mL, 4.28 mmol). The cooling bath was removed and the mixture was stirred at 23° C. for 2 h. The mixture was filtered to remove the white precipitate, and the filtrate was treated with a 2 M THF solution of lithium borohydride (1.944 mL, 3.89 mmol) resulting in vigorous gas evolution. The mixture was stirred at room temperature for 2 h. Brine (25 mL) was added. The mixture was extracted with ethyl acetate (3×25 mL). The combined organic extracts were dried (MgSO4), filtered, then concentrated under vacuum. The residue was purified by silica gel flash column chromatography to give (S)-tert-butyl 4,4,4-trifluoro-1-hydroxybutan-2-ylcarbamate (0.80 g) as a white solid. This solid material was treated with 4 M HCl in dioxane (10 mL) for 60 min then concentrated to give the title compound (0.54 g) as a white solid. 1H NMR (400 MHz, CD3OD) δ 2.55-2.79 (m, 2H), 3.42 (bs, 1H), 3.54 (dd, J=11.6, 5.6 Hz, 1H), 3.66 (dd, J=11.6, 3.9 Hz, 1H), 3.53 (bs, 1H), 8.27 (bs, 3H).

1. customThe cooling bath was removed
2. filtrationThe mixture was filtered
3. customto remove the white precipitate
4. customresulting in vigorous gas evolution
5. stirringThe mixture was stirred at room temperature for 2 h
6. extractionThe mixture was extracted with ethyl acetate (3×25 mL)
7. dry with materialThe combined organic extracts were dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customThe residue was purified by silica gel flash column chromatography

ORD record

ord-76f467e9635c45ef919ce076d910bf6f

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778950B2