Diethyl Malonate → HCID 22337492, compound

Sodium metal (3.2 g) was dissolved in ethanol (50 ml) under a nitrogen atmosphere at room temperature. A solution of diethyl malonate (56.4 ml) in ethanol (50 ml) was added dropwise, followed by a solution of 4-benzenesulfonyloxy-piperidine-1-carboxylic acid benzyl ester (31.88 g) in ethanol (50 ml), also added dropwise. The mixture was heated to reflux for 16 h then the solvent was removed under reduced pressure. The residue was partitioned between water (100 ml) and diethyl ether (100 ml) and the aqueous washed with further diethyl ether (60 ml). The combined organics were washed with 10% citric acid solution (50 ml), water (50 ml) and brine (50 ml). After drying (Na2SO4) and filtering the solvent was removed under reduced pressure to leave a yellow liquid. Half of this crude diester was taken and dissolved in methanol (150 ml) and water (50 ml). Lithium hydroxide monohydrate (18.14 g) was added slowly and the reaction left to stir at room temperature for 16 h then the methanol was removed under reduced pressure. The aqueous was washed with diethyl ether (3×40 ml), acidified to pH=3 with citric acid and extracted with ethyl acetate (2×40 ml). The combined organics were washed with water (2×40 ml) and brine (40 ml), dried (Na2SO4), filtered and evaporated under reduced pressure to give the title compound (8.29 g, 56%) as a white crystalline solid.

1. additionalso added dropwise
2. temperatureThe mixture was heated
3. temperatureto reflux for 16 h
4. customthe solvent was removed under reduced pressure
5. customThe residue was partitioned between water (100 ml) and diethyl ether (100 ml)
6. washthe aqueous washed with further diethyl ether (60 ml)
7. washThe combined organics were washed with 10% citric acid solution (50 ml), water (50 ml) and brine (50 ml)
8. dry with materialAfter drying (Na2SO4)
9. filtrationfiltering the solvent
10. customwas removed under reduced pressure
11. customto leave a yellow liquid
12. waitthe reaction left
13. customthe methanol was removed under reduced pressure
14. washThe aqueous was washed with diethyl ether (3×40 ml)
15. extractionextracted with ethyl acetate (2×40 ml)
16. washThe combined organics were washed with water (2×40 ml) and brine (40 ml)
17. dry with materialdried (Na2SO4)
18. filtrationfiltered
19. customevaporated under reduced pressure

ORD record

ord-4f34130b2b0345eeb2474a5e84e45f9f

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06506773B2