Dimethyl methylphosphonate → Dimethyl 2-oxo-4-(3,4-dimethoxyphenyl)butylphosphonate

HRID 569640Notes

Reaction equation

C([Li])CCC.[CH3:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9].[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH2:23][CH2:24][C:25](OC)=[O:26])[CH:18]=[CH:19][C:20]=1[O:21][CH3:22]>CCCCCC.O1CCCC1.[Cl-].[Na+]>[O:26]=[C:25]([CH2:24][CH2:23][C:17]1[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:15]([O:14][CH3:13])[CH:16]=1)[CH2:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9]

Participants

Conditions

Temperature: -78 °C

Procedure

To a mixture cooled at -78° C. of 50 ml of 2.1M n-butyl lithium solution in hexane and 100 ml of tetrahydrofuran, was added dropwise 12.4 g of dimethyl methylphosphonate. The mixture was stirred at -78° C. for 30 minutes, and thereafter 22.4 g of methyl 3-(3,4-dimethoxyphenyl)propionate [synthesized from 3,4-dimethoxycinnamic acid in 2 steps: (a) esterification (HCl--CH3OH) and (b) reduction (Pd/C--H2)] and 100 ml of tetrahydrofuran were added dropwise to the mixture. Then, the reaction was continued at -78° C. for 22 hours. The reaction mixture was poured in 500 ml of saturated aqueous sodium chloride solution. After neutralization and extraction with dichloromethane, the extract was dried and concentrated to give crude product. By purification of the crude product by means of column chromatography (silica gel/hexane:ethyl acetate=1:4), 9.0 g of the above caption compound was obtained.

Workup

waitThen, the reaction was continued at -78° C. for 22 hours
extractionAfter neutralization and extraction with dichloromethane
customthe extract was dried
concentrationconcentrated
customto give crude product
customBy purification of the crude product by means of column chromatography (silica gel/hexane:ethyl acetate=1:4)

Sources & evidence

ORD record: ord-8709608733304e8d8035a1795b7ee7de
Source dataset: uspto-grants-1988_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04733002

Reaction notes

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