Phosphorus trichloride → Risedronate

HRID 2218543Notes

Reaction equation

HRID 2218543 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]([OH:11])=O)[CH:3]=1.[P:12]([OH:15])([OH:14])[OH:13].P(Cl)(Cl)Cl>S1(CCCC1)(=O)=O>[CH:6]1[CH:7]=[N:2][CH:3]=[C:4]([CH2:8][C:9]([P:12]([OH:15])([OH:14])=[O:13])([P:12]([OH:15])([OH:14])=[O:13])[OH:11])[CH:5]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 107909Phosphorous acidHCID 27237243-Pyridineacetic acid, hydrochloride (1:1)

Product 1

HCID 5245Risedronate

Reagents, catalysts & solvents 1

HCID 31347SulfolaneSolvent

Conditions

Temperature
75 °C

Procedure

A suspension of 3-pyridylacetic acid hydrochloride (50 g, 0.288 mol) and phosphorous acid (35.4 g, 0.432 mol) in sulfolane (180 ml) is heated to 75° C. for 30 min. The mixture is cooled to 35-40° C. and then gradually introduced phosphorous trichloride (85.6 ml, 0.98 mol) while maintaining the temperature between 35-45° C. The mixture is heated to 63-67° C. for 3 hours whereby a thick white mass results. It is then cooled to 0-5° C. and quenched by slow addition of water (500 ml) at 0-5° C. over a period of 1 hour. The resulting clear solution is charcoalized and heated at 100° C. for 3 hrs, cooled to ambient temperature and then cooled 0-5° C. After stirring for 2 hrs at 0-5° C. the crystallized product is filtered, washed sequentially with chilled water (100 ml), rectified spirit (75 ml) and dried in air oven at 55-60° C. until loss on drying is less than 0.5% w/w. Yield 60.4 g, (70.47%), appearance: white crystalline solid, purity >99.0%.

Workup

  1. temperatureThe mixture is cooled to 35-40° C.
  2. temperatureThe mixture is heated to 63-67° C. for 3 hours whereby a thick white mass
  3. customresults
  4. temperatureIt is then cooled to 0-5° C.
  5. customquenched by slow addition of water (500 ml) at 0-5° C. over a period of 1 hour
  6. temperatureheated at 100° C. for 3 hrs
  7. temperaturecooled to ambient temperature
  8. temperaturecooled 0-5° C
  9. filtrationis filtered
  10. washwashed sequentially with chilled water (100 ml), rectified spirit (75 ml)
  11. customdried in air oven at 55-60° C. until loss
  12. customon drying

Sources & evidence

ORD record
ord-0ee5a552ec8742fba98bd26ab64fc816
Source dataset
uspto-grants-2008_08
Patent number
US07411087B2

Reaction notes

Loading…