Triethylamine → tert-Butyl N-allyl-N-[2-(methoxy(methyl)amino)-2-oxo-ethyl]carbamate

Temperature

0 °C

2-(Allyl(tert-butoxycarbonyl)amino)acetic acid (49.6 g, 156 mmol), tetrahydrofuran (600 mL), and triethylamine (36.3 g, 359 mmol) is added to an Erlenmeyer flask and the mixture is cooled to 0° C. Pivaloyl chloride (31 g, 253 mmol) is added drop wise and the reaction is stirred at room temperature for 3 hours and then cooled to 0° C. N,O-dimethylhydroxylamine hydrochloride (28 g, 283 mmol), triethylamine (33 mL, 237 mmol) and tetrahydrofuran (400 mL) are then added. The ice bath is removed and the reaction is stirred at room temperature for 3 hours. The mixture is concentrated under reduced pressure. The resulting residue is dissolved in water (300 mL) and extracted with ethyl acetate (2×300 mL). The organic phases are combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by silica gel flash chromatography, eluting with hexane/acetone (1:0) to hexane/acetone (1:1) to give the title compound (32 g, 54%). 1H NMR (CDCl3) mixture of two rotamers (60:40) δ 1.42, 1.44 (s, 9H), 3.16, 3.17 (s, 3H), 3.66, 3.69 (s, 3H), 3.88-3.98 (m, 2H), 4.01, 4.11 (s, 2H), 5.10-5.18 (m, 2H), 5.73-5.85 (m, 1H).

1. temperaturecooled to 0° C
2. customThe ice bath is removed
3. stirringthe reaction is stirred at room temperature for 3 hours
4. concentrationThe mixture is concentrated under reduced pressure
5. dissolutionThe resulting residue is dissolved in water (300 mL)
6. extractionextracted with ethyl acetate (2×300 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto give a residue
11. customThe residue is purified by silica gel flash chromatography
12. washeluting with hexane/acetone (1:0) to hexane/acetone (1:1)

ORD record

ord-41a0651615484448bce4ee277ea9cd1b

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889856B2