Diisopropylamine → Methyl 2-hydroxy-3-cyclopropyl-3-methylbutanoate

온도

-78 °C

To a stirred solution of diisopropylamine (4.9 mL, 35 mmol) in dry THF (100 mL) at 0° C. under inert atmosphere was added n-butyllithium (14 mL, 35 mmol) dropwise over a period of 5 min. The solution was cooled to −78 ° C. and methyl 3-cyclopropyl-3-methylbutanoate (5.0 g, 32) was added dropwise over a period of 5 min. The solution was stirred at −78 ° C. for 1 h at which time (+)-camphorsulfonyloxaziridine (9.0 g, 39 mmol) was added all at once. The resulting suspension was stirred at −78 ° C. for 30 min and then allowed to warm to ambient temperature over 30 min. EtOAc (100 mL) and saturated aqueous ammonium chloride (50 mL) were added and the organic layer was separated and washed with water (50 mL), dried (MgSO4), and filtered. The solvents were removed under reduced pressure and the resulting oily solid was stirred in ether (50 mL) for 30 min. The solid was removed by filtration and the filtrate solvent was removed under reduced pressure. The residue was purified by flash column chromatography using a gradient elution of 10% to 14% EtOAc in hexanes to give methyl 2-hydroxy-3-cyclopropyl-3-methylbutanoate as a colorless liquid. TLC Rf=0.4 (12% EtOAc-hexanes); HPLC RT=2.72 min (Method A); 1H NMR 400 MHz, CDCl3, 3.92 ppm ((d, J=7.9 Hz, 1H), 3.79 ppm (s, 3H), 2.79 ppm (d, J=7.9 Hz, 1H), 0.84 ppm (s, 3H), 0.83 ppm (m, 1H), 0.80 ppm (s, 3H), 0.32 ppm (m, 2H), 0.20 ppm (m, 2H)

1. additionwas added all at once
2. temperatureto warm to ambient temperature over 30 min
3. customthe organic layer was separated
4. washwashed with water (50 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customThe solvents were removed under reduced pressure
8. stirringthe resulting oily solid was stirred in ether (50 mL) for 30 min
9. customThe solid was removed by filtration
10. customthe filtrate solvent was removed under reduced pressure
11. customThe residue was purified by flash column chromatography
12. washa gradient elution of 10% to 14% EtOAc in hexanes

ORD 기록

ord-57dc2cb540e541b6a7a1a38ae912e849

출처 데이터셋

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06528503B2