CID 406 → Dimethyl [2-oxo-3-(thiophen-2-yl)propyl]phosphonate

HRID 867125Notes

Reaction equation

HRID 867125 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].P(=O)([O-])[O-].C([Li])CCC.[S:17]1[CH:21]=[CH:20][CH:19]=[C:18]1[CH2:22][C:23](OC)=[O:24]>O1CCCC1.CCCCCC.C(O)(=O)C>[O:24]=[C:23]([CH2:22][C:18]1[S:17][CH:21]=[CH:20][CH:19]=1)[CH2:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4]

Participants

8

Reactant 4

HCID 406CID 406HCID 12958Dimethyl methylphosphonateHCID 88055Methyl thiophen-2-acetateHCID 178418339Butyllithium

Product 1

HCID 21329763Dimethyl [2-oxo-3-(thiophen-2-yl)propyl]phosphonateYield 12.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A solution of 37.2 g (0.3 mole) dimethyl methylphosphonate (Aldrich) in 400 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 194 ml of 1.6 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 18 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 23.4 g (0.15 mole) methyl 2-(2-thienyl)acetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 3.5 hours at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 6 ml acetic acid and rotary evaporated to a white gel. The gelatinous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3× the combined organic extracts were backwashed (50 ml H2O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 150°-52° (<0.5 mm) to give 4.8 g dimethyl 2-oxo-3(2-thienyl)propylphosphonate (2a).

Workup

  1. customthe reaction temperature less than -70° (20 minutes)
  2. waitAfter 3.5 hours at -78° the reaction mixture was allowed
  3. customrotary evaporated to a white gel
  4. extractionthe aqueous phase extracted with 100 ml portions of chloroform (3× the combined organic extracts
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated (water aspirator) to a crude residue
  7. distillationdistilled

Sources & evidence

ORD record
ord-5f5f245b2c534b698a0231f1227708ec
Source dataset
uspto-grants-1978_07
Patent number
US04102894

Reaction notes

Loading…