Sodium Bicarbonate → S-Ethyl 3-(diethylphosphono)propionyloxymethyl carbonothioate

HRID 1397126Notes

Reaction equation

HRID 1397126 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].C([O-])(O)=O.[Na+].[C:19](=[O:26])([O:23][CH2:24]I)[S:20][CH2:21][CH3:22]>O.C(Cl)Cl>[C:19](=[O:26])([O:23][CH2:24][O:12][C:11](=[O:13])[CH2:10][CH2:9][P:4]([O:3][CH2:1][CH3:2])([O:6][CH2:7][CH3:8])=[O:5])[S:20][CH2:21][CH3:22]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27737363-(Diethylphosphono)propanoic acidHCID 11436522(Ethylsulfanyl)(iodomethoxy)methanone

Product 1

HCID 86666539S-Ethyl 3-(diethylphosphono)propionyloxymethyl carbonothioateYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of 3-(diethylphosphono)propanoic acid (79, 1.0 g, 4.76 mmol) in H2O (12 mL) and CH2Cl2 (12 mL) was added NaHCO3 (1.0 g, 11.9 mmol) and TBAHSO4 (1.62 g, 4.76 mmol). After stirring for 20 min, S-ethyl O-iodomethyl carbonothioate (1.17 g, 4.76 mmol) in CH2Cl2 (2 mL) was added. The biphasic reaction was stirred vigorously for 4 h 20 min and was diluted with water and CH2Cl2. The layers were separated, the organic layer was washed with H2O, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution, dried over MgSO4, filtered and concentrated to dryness. The crude product was triturated with Et2O and the solids were removed by filtration and rinsed with small portions of Et2O. After concentration, the combined filtrates were purified by flash chromatography on a Biotage™ flash chromatography system, using EtOAc as the eluent, to yield compound 80 (1.29 g, 83%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 1.30-1.65 (m, 9H), 2.03-2.12 (m, 2H), 2.64-2.71 (m, 2H), 2.90 (q, J=7.4 Hz, 2H), 4.06-4.14 (m, 4H), 5.82 (s, 2H). 31P NMR (162 MHz, CDCl3) δ 30.45 (s).

Workup

  1. customThe biphasic reaction
  2. stirringwas stirred vigorously for 4 h 20 min
  3. customThe layers were separated
  4. washthe organic layer was washed with H2O, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was triturated with Et2O
  9. customthe solids were removed by filtration
  10. washrinsed with small portions of Et2O
  11. concentrationAfter concentration
  12. customthe combined filtrates were purified by flash chromatography on a Biotage™ flash chromatography system

Sources & evidence

ORD record
ord-d40f576338f0445b98665f0d7e9971fd
Source dataset
uspto-grants-2014_12
Patent number
US08901072B2

Reaction notes

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