Dimethylformamide → Diethyl (3-hydroxypropyl)phosphonate

HRID 728235Notes

Reaction equation

HRID 728235 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][CH2:10][CH2:11]Br)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].CN(C=[O:17])C>>[CH2:1]([O:3][P:4]([CH2:9][CH2:10][CH2:11][OH:17])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

3

Reactant 2

HCID 6228DimethylformamideHCID 283500Diethyl (3-bromopropyl)phosphonate2×

Product 1

HCID 12594218Diethyl (3-hydroxypropyl)phosphonate

Procedure

Diethyl-3-hydroxypropylphosphonate (steps 1 and 2) is prepared from diethyl-3-bromopropylphosphonate. Diethyl-3-bromopropylphosphonate (12.0 g, 46 mmol), prepared by the method of Eberhard, A., et al, J Am Chem Soc (1965) 87:253-260) was stirred with 12.0 g NaOAc.3H2O in 125 ml DMF heated in a steam bath. The reaction was evaporated to dryness in vacuo after 2 hours and partitioned between H2O and EtOAc. extracting the aqueous layer five times. The ethyl acetate extract was washed once with brine, dried with Na2SO4, filtered, and evaporated to dryness in vacuo to yield 9.8 g light yellow oil (89%). 1H NMR (CDCl3) δ1.3 (tr, 6 H), 1.5-2.0 (m, 4 H), 2.03 (s, 3 H), 4.1 (dq, 6 H): thin-layer chromatography on SiGF developed with 2:1 EtOAc:CH2Cl2 gave Rf 0.30. The isolated diethyl-3-acetoxypropylphosphonate (9.8 g, 41 mmol) in 200 ml abs. EtOH was stirred with 30 ml Dowex 50 (H+) which had been rinsed three times each with H2O and EtOH. After 41/2 days at room temperature, another 10 ml of similarly prepared resin was added. Six hours later, the reaction was filtered and evaporated in vacuo. The quantitative yield of yellow oil was purified by dry column chromatography on 400 g silica packed in a 2.75-inch flat diameter nylon tube. The column was eluted with 1:9 MeOH:EtOAc and the appropriate fractions were cut and slurried with 1:1 MeOH:EtOAc. Filtration and evaporation in vacuo afforded 5.33 g (66%) pale yellow oil, which is the diethyl ester of 3-hydroxypropyl phosphonic acid. 1H NMR (CDCl3, D2O): δ1.3 (tr, 6 H), 1.6-2.08 (m, 4 H), 3.67 (tr. 2 H), 4.13 (dq. 4 H); thin-layer chromatography on SiGF developed with 1:9 MeOH:EtOAc gave an Rf of 0.57.

Workup

  1. temperatureheated in a steam bath
  2. customThe reaction was evaporated to dryness in vacuo after 2 hours
  3. custompartitioned between H2O and EtOAc
  4. extractionextracting the aqueous layer five times
  5. extractionThe ethyl acetate extract
  6. washwas washed once with brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-4b3bffad36a84db193997d06874aacbd
Source dataset
uspto-grants-1991_09
Patent number
US05047533

Reaction notes

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