Benzoyl chloride → HCID 20156122, compound

HRID 986775Notes

Reaction equation

HRID 986775 reaction equation
[NH2:1][CH2:2][CH2:3][P:4]([CH2:7][C:8]([OH:10])=[O:9])([OH:6])=[O:5].C(N(CC)CC)C.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[NH4+].[OH-].O>O1CCOCC1.O.C(O)(C)C>[C:18]([NH:1][CH2:2][CH2:3][P:4]([CH2:7][C:8]([OH:10])=[O:9])([OH:6])=[O:5])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 20156116HCID 20156116, compoundHCID 86589665Water ammonium hydroxide

Product 1

HCID 20156122HCID 20156122, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of [(2-aminoethyl)hydroxyphosphinyl]acetic acid (0.75 g., 4.49 mmole) in a mixture of dioxane (5 ml.) and water (5 ml.) was cooled in an ice bath and treated with triethylamine (2.0 ml., 14.5 mmole). A clear solution was obtained. The mixture was then treated with benzoyl chloride (0.65 ml., 5.6 mmole) dropwise over a 5 minute period. After stirring at 0° for one hour, the mixture was evaporated to dryness. The residue was taken up in saturated sodium bicarbonate (20 ml.) and washed with ethyl acetate. The aqueous phase was acidified with concentrated hydrochloric acid (pH 1) and extracted with dichloromethane. The dichloromethane extracts were discarded and the aqueous phase evaporated to a small volume. This was then applied to an AG 1-X8 (acetate form) column (30 ml. bed volume) eluting first with water then with 5% acetic acid-water then 1N hydrochloric acid. The product eluted with 1N hydrochloric acid. Fractions containing the product were combined, evaporated to dryness, taken up in water, and lyophilized. The crude product (0.9 g.) was chromatographed on an HP-20 column (1 inch diameter column, 200 ml. bed volume) eluting with a linear gradient of water-acetonitrile (0→100%) at a flow rate of 5 ml./min., collecting 5 ml. fractions. The fractions containing the desired product (Tlc) were combined, evaporated, taken up in water, millipore filtered, and lyophilized to give 0.72 g. of [[(2-benzoylamino)ethyl]hydroxyphosphinyl]acetic acid as a white solid; m.p. 54°-57°; Rf (isopropanol/conc. NH4OH/water; 7:2:1)=0.42.

Workup

  1. temperaturewas cooled in an ice bath
  2. customA clear solution was obtained
  3. customthe mixture was evaporated to dryness
  4. washwashed with ethyl acetate
  5. extractionextracted with dichloromethane
  6. customthe aqueous phase evaporated to a small volume
  7. washeluting first with water
  8. washThe product eluted with 1N hydrochloric acid
  9. additionFractions containing the product
  10. customevaporated to dryness
  11. customThe crude product (0.9 g.) was chromatographed on an HP-20 column (1 inch diameter column, 200 ml. bed volume)
  12. washeluting with a linear gradient of water-acetonitrile (0→100%) at a flow rate of 5 ml
  13. custom, collecting 5 ml
  14. additionThe fractions containing the desired product (Tlc)
  15. customevaporated
  16. filtrationmillipore filtered
  17. customto give 0.72 g

Sources & evidence

ORD record
ord-cc89c6d5f14a4b4fb64c4a913a7a7cb4
Source dataset
uspto-grants-1987_12
Patent number
US04716155

Reaction notes

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