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

HRID 1076175Notes

Reaction equation

HRID 1076175 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 (3x) 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 (3x) the combined organic extracts
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated (water aspirator) to a crude residue
  7. distillationdistilled

Sources & evidence

ORD record
ord-a46d2ec0aed540eaa495d169060d14d5
Source dataset
uspto-grants-1976_05
Patent number
US03956284

Reaction notes

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