Formaldehyde → Exemestane impurity B -F

HRID 1919308Notes

Reaction equation

HRID 1919308 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 traspires. 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 traspires
  5. customSaid product is collected
  6. washwashed
  7. customdried

Sources & evidence

ORD record
ord-cf6165c1d3ae48178fc638958a95f014
Source dataset
uspto-grants-2012_05
Patent number
US08168621B2

Reaction notes

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