Ethyl chloroformate → HCID 11075646, Verbindung

Temperatur

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 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 column chromatography

ORD-Eintrag

ord-e3706f2fee5b416ea4e4391e385c0b98

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08778950B2