Formaldehyde → Exemestane impurity B -F

HRID 469155Notes

Reaction equation

HRID 469155 reaction equation
N1([CH:6]2[C@@:23]3([CH3:24])[C:10](=[CH:11][CH2:12][C@@H:13]4[C@@H:22]3[CH2:21][CH2:20][C@@:18]3([CH3:19])[C@H:14]4[CH2:15][CH2:16][C:17]3=[O:25])[CH:9]=[C:8](N3CCCC3)[CH2:7]2)CCCC1.[CH2:31]=[O:32].S(=O)(=O)(O)[OH:34]>ClCCl>[OH:32][CH2:31][CH:11]1[C:10]2[C@:23]([CH3:24])([CH:6]=[CH:7][C:8](=[O:34])[CH:9]=2)[C@@H:22]2[C@H:13]([C@H:14]3[C@@:18]([CH2:20][CH2:21]2)([CH3:19])[C:17](=[O:25])[CH2:16][CH2:15]3)[CH2:12]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 9953300HCID 9953300, compound

Product 1

HCID 11681199Exemestane impurity B -F

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The resulting 1,3-dipyrrolidinoandrosta-3,5-diene-17one is then mixed in amount of 1 equivalent, with 2.6 equivalents formalin (formaldehyde) in 10 ml dichloromethane/g at room temperature. The reaction mixture is then acidified to a pH of about 2 with 2% sulfuric acid solution. Accordingly, an organic layer is formed, which is washed with 2% sulfuric acid and 1:1 water/brine. Solvent exchange into toluene (approximately 10 ml/g) is then carried out wherein the product crystallizes as toluene exchange transpires. Said product is collected washed and dried to provide 6-hydroxymethyl-androsta-1,4-diene-3,17 dione. One of ordinary skill in the art can further modify the stereochemistry at position 6, if so desired by employing known techniques in the art.

Workup

  1. customg at room temperature
  2. customAccordingly, an organic layer is formed
  3. washwhich is washed with 2% sulfuric acid and 1:1 water/brine
  4. customcrystallizes as toluene exchange transpires
  5. customSaid product is collected
  6. washwashed
  7. customdried

Sources & evidence

ORD record
ord-70ac340583f14c6886b26224436f0e3c
Source dataset
uspto-grants-2014_01
Patent number
US08629130B2

Reaction notes

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