Phosphorus trichloride → Minodronic acid

HRID 253729Notes

Reaction equation

HRID 253729 reaction equation
[N:1]1[CH:2]=[C:3]([CH2:10][C:11]([OH:13])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[P:14]([OH:17])([OH:16])[OH:15].P(Cl)(Cl)Cl>O1CCOCC1>[CH:7]1[CH:8]=[CH:9][N:4]2[C:3]([CH2:10][C:11]([P:14]([OH:17])([OH:16])=[O:15])([P:14]([OH:17])([OH:16])=[O:15])[OH:13])=[CH:2][N:1]=[C:5]2[CH:6]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 87284Imidazo(1,2-a)pyridine-3-acetic acidHCID 107909Phosphorous acid

Product 1

HCID 130956Minodronic acidYield 52.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
92.5 °C

Procedure

Imidazo[1,2-a]pyridin-3-yl acetic acid (46 gm), phosphorous acid (75 gm) and 1,4-Dioxane (900 mL) was taken in a four necked round bottom flask fitted with an addition funnel, mechanical stirrer, condenser and thermometer pocket and allowed to stir at 90-95° C. Phosphorus trichloride (130 gm) was then added to reaction mixture and allowed to heat at 90-95° C. The reaction mixture was cooled and distilled water (450 mL) was added to it. The reaction mixture was further heated to 90-95° C. It was then cooled and acetone (1400 mL) was added to it. The solution was further cooled to 0-5° C. and stirred for 4-5 hrs. The precipitated solid was filtered and dried under vacuum to give 44 gm of product.

Workup

  1. customfitted with an addition funnel, mechanical stirrer, condenser
  2. temperatureto heat at 90-95° C
  3. temperatureThe reaction mixture was cooled
  4. distillationdistilled water (450 mL)
  5. additionwas added to it
  6. temperatureThe reaction mixture was further heated to 90-95° C
  7. temperatureIt was then cooled
  8. additionacetone (1400 mL) was added to it
  9. temperatureThe solution was further cooled to 0-5° C.
  10. stirringstirred for 4-5 hrs
  11. filtrationThe precipitated solid was filtered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-244888b077e44a39b46afb91d4ce1f4d
Source dataset
uspto-grants-2011_01
Patent number
US07872144B2

Reaction notes

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