Diisopropylamine → HCID 11206584, compound

To a solution of diisopropylamine (1.675 mL, 11.75 mmol) in THF (10 mL) was added n-BuLi/hexane (4.70 mL, 11.75 mmol) dropwise at −78° C. The reaction mixture was stirred in the bath for 5 min and then stirred in ice bath for 30 min. The reaction mixture was added dropwise a solution of methyl isobutyrate (1 g, 9.79 mmol) in THF (5 mL) at −78° C. The reaction mixture was stirred at −78° C. for 2 hr. The solution of picolinaldehyde (1.258 g, 11.75 mmol) in THF (2 mL) was added dropwise at −78° C. Then the solution was allowed to warm to room temperature and stirred for 1 hr. The reaction was quenched with NH4Cl, then diluted with EtOAc. Then organic phase was washed with sat. NaHCO3, water, sat. NaCl, dried over anhydrous Na2SO4, and concentrated to yield an oil. The crude was purified by silica chromatography with 0-100% EtOAc/Hex to yield methyl 3-hydroxy-2,2-dimethyl-3-(pyridin-2-yl)propanoate (1.0 g) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) ppm 8.61-8.44 (m, 1H), 7.66 (td, J=7.7, 1.8 Hz, 1H), 7.26-7.12 (m, 2H), 4.96 (d, J=7.5 Hz, 1H), 4.67 (d, J=7.5 Hz, 1H), 3.74 (s, 3H), 1.18 (s, 3H), 1.10 (s, 3H).

1. stirringstirred in ice bath for 30 min
2. stirringThe reaction mixture was stirred at −78° C. for 2 hr
3. stirringstirred for 1 hr
4. customThe reaction was quenched with NH4Cl
5. additiondiluted with EtOAc
6. washThen organic phase was washed with sat. NaHCO3, water, sat. NaCl
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated
9. customto yield an oil
10. customThe crude was purified by silica chromatography with 0-100% EtOAc/Hex

ORD record

ord-f5a72f9232a74f1db5130fecc7798ade

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09326973B2