Methyl valerate → Dimethyl (2-oxohexyl)phosphonate

To a solution of dimethyl methylphosphonate (3.25 mL, 30 mmol) in anhydrous THF (30 mL), cooled at −78° C. was added n-BuLi (1.6 M in hexane, 20.6 mL, 33 mmol). The mixture was stirred for 30 minutes at this temperature under nitrogen. Methyl valerate (2.0 mL, 15 mmol) was added dropwise for 10 minutes. The mixture was stirred for 2 hours at −78° C., gradually was warm to room temperature. The mixture was quenched with addition of 1N HCl to pH 4-5. The organic layer was separated, washed with brine and dried over MgSO4. The residue was purified through flash chromatography on silica gel (MeOH/DCM 2/98) to give the product (3.0 g) with colorless oil in 96% yield. 1H NMR (CDCl3) δ 0.848 (t, J=7.3 Hz, 3H), 1.28 (m, 2H), 1.52 (m, 2H), 2.57 (t, J=2.4 Hz, 2H) 3.074 (d, J=21 Hz, 2H), 3.760 (s, 3H), 3.762 (s, 3H).

1. stirringThe mixture was stirred for 2 hours at −78° C.
2. customThe mixture was quenched with addition of 1N HCl to pH 4-5
3. customThe organic layer was separated
4. washwashed with brine
5. dry with materialdried over MgSO4
6. customThe residue was purified through flash chromatography on silica gel (MeOH/DCM 2/98)

ORD record

ord-af67435dd7f345b98ab2dfc2d3e628f0

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419999B2