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

HRID 1386806Notes

Reaction equation

HRID 1386806 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-butyllithium 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/i-PrOH 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. NaCl (50 1L) and CH2Cl2 (200 mL). The aq. layer was extracted with CH2Cl2 (2×100 1L). The combined organic layers were dried (Na2SO4) decanted, and evaporated. Purification by flash column chromatography on silica gel, eluting with EtOAc followed by 97:3 v/v CH2Cl2/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/EtOAc/CH3OH gave 1.15 g of the title compound. For the title compound: 1H NMR (500 MHz, CDCl3) δ 9.26-9.20 (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/i-PrOH bath
  2. customThe reaction was quenched with saturated aq. NH4Cl (50 mL)
  3. custompartitioned between saturated aq. NaCl (50 1L) and CH2Cl2 (200 mL)
  4. extractionThe aq. layer was extracted with CH2Cl2 (2×100 1L)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. customdecanted
  7. customevaporated
  8. customPurification by flash column chromatography on silica gel
  9. washeluting with EtOAc
  10. customgave material
  11. additioncontaining some residual impurity
  12. customFurther 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/EtOAc/CH3OH

Sources & evidence

ORD record
ord-99b5b9ca2c814c84b7ef3bae554e12e4
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

Loading…