Butanal → Budesonide

HRID 743496Notes

Reaction equation

HRID 743496 reaction equation
[C:1]1(C)[CH:6]=CC(S(O)(=O)=O)=[CH:3][CH:2]=1.[CH3:12][C@@:13]12[C@@:21]([OH:26])([C:22]([CH2:24][OH:25])=[O:23])[C@H:20]([OH:27])[CH2:19][C@H:18]1[C@@H:17]1[CH2:28][CH2:29][C:30]3[C@@:36]([CH3:37])([C@H:16]1[C@@H:15]([OH:38])[CH2:14]2)[CH:35]=[CH:34][C:32](=[O:33])[CH:31]=3.C(=O)CCC>C(#N)C>[CH3:6][CH2:1][CH2:2][CH:3]1[O:26][C@:21]2([C:22]([CH2:24][OH:25])=[O:23])[C@@H:20]([CH2:19][C@@H:18]3[C@:13]2([CH3:12])[CH2:14][C@H:15]([OH:38])[C@H:16]2[C@H:17]3[CH2:28][CH2:29][C:30]3[C@:36]2([CH3:37])[CH:35]=[CH:34][C:32](=[O:33])[CH:31]=3)[O:27]1

Participants

5

Reactant 3

HCID 261ButanalHCID 6101p-Toluenesulfonic acidHCID 1104705616alpha-Hydroxyprednisolone

Product 1

HCID 5281004Budesonide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The reaction is carried out in a nitrogen atmosphere. 15,4 g p-toluenesulphonic acid is dissolved into 200 ml acetonitrile. To the solution 50,0 g 16α-hydroxyprednisolone and 17.6 ml butanal are added. The temperature rises to 25° C. After 30 min most of the material is dissolved. Shortly thereafter the product starts to crystallize. After 3 hours the reaction is stopped by the addition of 75 ml aqueous saturated sodium hydrogen carbonate solution, whereupon the product crystallizes. The dried product is dissolved in methylene chloride and methanol and is crystallized by the addition of ligroine (b.p. 40-65) giving crude budesonide.

Workup

  1. customrises to 25° C
  2. dissolutionAfter 30 min most of the material is dissolved
  3. customto crystallize
  4. additionAfter 3 hours the reaction is stopped by the addition of 75 ml aqueous saturated sodium hydrogen carbonate solution, whereupon the product
  5. customcrystallizes
  6. dissolutionThe dried product is dissolved in methylene chloride
  7. custommethanol and is crystallized by the addition of ligroine (b.p. 40-65)

Sources & evidence

ORD record
ord-57acb4105cee464aa6ed4e5a8c7b16d7
Source dataset
uspto-grants-1996_09
Patent number
US05556964

Reaction notes

Loading…