(R)-(-)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-methylpyrazine → (2R,5S)-2-Isopropyl-3,6-dimethoxy-5-((S)-2-phenyl-butyl)-2,5-dihydro-pyrazine

A solution of (R)-(−)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-methylpyrazine (4.25 g, 23.1 mmol) in tetrahydrofuran (30 ml) was cooled to −78° C., then n-butyllithium (1.6 M in hexane, 15.1 ml, 24.2 mmol) was added and the mixture was stirred for 1 hour. A solution of ((R)-1-iodomethyl-propyl)-benzene (6.30 g, 24.2 mmol) in tetrahydrofuran (30 ml) was added dropwise over 30 min and the mixture was stirred overnight while being allowed to warm slowly from −70° C. to room temperature. The reaction was quenched by addition of saturated aqueous ammonium chloride solution and the mixture was extracted with ether. The organic layer was separated, washed with saturated brine, then dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (SiO2, heptane/EtOAc) to yield a light yellow oil (4.69 g, 64%); MS (ISP): 317.0 ([M+H]+).

1. stirringthe mixture was stirred overnight
2. temperatureto warm slowly from −70° C. to room temperature
3. customThe reaction was quenched by addition of saturated aqueous ammonium chloride solution
4. extractionthe mixture was extracted with ether
5. customThe organic layer was separated
6. washwashed with saturated brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography (SiO2, heptane/EtOAc)

ORD record

ord-490b214d8d0f4ca2b8803abcefe4c533

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604061B2