Methyl Nicotinate → Dimethyl [2-oxo-2-(pyridin-3-yl)ethyl]phosphonate

HRID 278257Notes

Reaction equation

HRID 278257 reaction equation
C([Li])CCC.[CH3:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9].[C:13](OC)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=1>C1COCC1>[O:20]=[C:13]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[CH2:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9]

Participants

5

Reactant 3

HCID 7151Methyl NicotinateHCID 12958Dimethyl methylphosphonateHCID 178418339Butyllithium

Product 1

HCID 18950746Dimethyl [2-oxo-2-(pyridin-3-yl)ethyl]phosphonateYield 90.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of n-butyl lithium in hexanes (9.0 mL, 1.6 M, 14 mmol) was added over 10 min. to a solution of dimethyl methylphosphonate (1.50 mL, 1.72 g, 13.8 mmol) in THF (60 mL) cooled in a dry ice/isopropanol bath. After 30 min., a solution of methyl nicotinate (757 mg, 5.52 mmol) in THF (6 mL) was added over 2 min. The solution was stirred in the cooling bath for 45 min. before being allowed to warm to 0° C. over 1 h. The reaction was quenched with saturated aq. NH4Cl (50 mL) and then partitioned between saturated aq. brine (50 mL) and methylene chloride (200 mL). The aq. layer was extracted with methylene chloride (2×100 mL). The combined organic layers were dried (sodium sulfate) decanted, and evaporated. Purification by flash column chromatography on silica gel, eluting with ethyl acetate followed by 97:3 v/v methylene chloride/CH3OH, gave material containing some residual impurity Further purification by flash column chromatography on silica gel, eluting with 50:50:5 v/v/v to 50:50:10 v/v/v toluene/ethyl acetate /CH3OH gave 1.15 g of the title compound. For the title compound: 1H NMR (500 MHz, CDCl3) δ9.26-9.20 (bs,1H), 8.83 (d, J=4, 1H), 8.34 (dt, J=8, 2, 1H), 7.70 (dd, J=8, 4, 1H), 3.82 (d, J=11, 6H), 3.67 (d, J=24, 2H).

Workup

  1. temperaturecooled in a dry ice/isopropanol bath
  2. customThe reaction was quenched with saturated aq. NH4Cl (50 mL)
  3. custompartitioned between saturated aq. brine (50 mL) and methylene chloride (200 mL)
  4. extractionThe aq. layer was extracted with methylene chloride (2×100 mL)
  5. dry with materialThe combined organic layers were dried (sodium sulfate)
  6. customdecanted
  7. customevaporated
  8. customPurification by flash column chromatography on silica gel
  9. washeluting with ethyl acetate
  10. customgave material
  11. additioncontaining
  12. customsome residual impurity Further purification by flash column chromatography on silica gel
  13. washeluting with 50:50:5 v/v/v to 50:50:10 v/v/v toluene/ethyl acetate /CH3OH

Sources & evidence

ORD record
ord-a52fcf48d7444e0597a022ed922185d4
Source dataset
uspto-grants-2002_03
Patent number
US06358979B1

Reaction notes

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