Pyridine → 12alpha-Acetoxypregna-1,4-dien-3-one-20-carbaldehyde

HRID 1607826Notes

Reaction equation

HRID 1607826 reaction equation
[OH:1][C@@H:2]1[C@@:22]2([CH3:23])[C@@H:14]([CH2:15][CH2:16][C@@H:17]2[CH:18]([CH:20]=[O:21])[CH3:19])[C@H:13]2[C@@H:4]([C@:5]3([CH3:25])[C:10]([CH2:11][CH2:12]2)=[CH:9][C:8](=[O:24])[CH:7]=[CH:6]3)[CH2:3]1.[C:26](Cl)(=[O:28])[CH3:27].N1C=CC=CC=1>C(Cl)Cl>[C:26]([O:1][C@@H:2]1[C@@:22]2([CH3:23])[C@@H:14]([CH2:15][CH2:16][C@@H:17]2[CH:18]([CH:20]=[O:21])[CH3:19])[C@H:13]2[C@@H:4]([C@:5]3([CH3:25])[C:10]([CH2:11][CH2:12]2)=[CH:9][C:8](=[O:24])[CH:7]=[CH:6]3)[CH2:3]1)(=[O:28])[CH3:27]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 1860288712alpha-Hydroxypregna-1,4-dien-3-one-20-carbaldehyde

Product 1

HCID 1863489012alpha-Acetoxypregna-1,4-dien-3-one-20-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

12α-Hydroxypregna-1,4-dien-3-one-20-carbaldehyde (34.2 g) was dissolved in 300 ml of methylene chloride. To the solution were added 23.6g of acetyl chloride and 27.7 g of pyridine, and the mixture was stirred atroom temperature for 5 hours. To the reaction mixture was added 300 ml of methylene chloride, the resulting solution was washed in sequence with diluted hydrochloric acid and water, and dried over anhydrous magnesium sulfate. Low-boiling fractions were distilled off from the solution under reduced pressure. There was thus obtained crude 12α-acetoxypregna-1,4-dien-3-one-20-carbaldehyde as a viscous substance. This crude product was dissolved in 300 ml of benzene, 21.3 g of piperidine was added to the solution, and the resulting mixture was refluxed for 3 hours while removing the byproduct water azeotropically with benzene. Low-boiling fractions were distilled off from the thus-obtained reaction mixture. There remained crude 12α-acetoxy-22-(N-piperidyl)bisnor-1,4,20(22)-cholatrien-3-one as a viscous substance, which was dissolved in 180 ml of pyridine. To the solution was added gradually at room temperature a mixture of 20.0 g of chromium trioxide and 250 ml of pyridine. After stirring the resulting mixture for one hour, 1 liter of benzene was added to the reaction mixture. The solid matter was filtered off, and diluted hydrochloric acid was added to the filtrate. After effecting benzene extraction to a sufficient extent, the benzene layer was washed in sequence with diluted hydrochloric acid and water. Low-boiling fractions were distilled off under reduced pressure, and the residue was purified by preparation liquidchromatography [column: Waters Associates' Prep LC/System 500, Prep PAK™500/SILICA; solvent system: isopropyl alcohol:n-hexane=20:80, v/v] to give 9.1 g of 12α-acetoxypregna-1,4-diene-3,20-dione as crystals.It has the following physical properties.

Workup

  1. washthe resulting solution was washed in sequence with diluted hydrochloric acid and water
  2. dry with materialdried over anhydrous magnesium sulfate
  3. distillationwere distilled off from the solution under reduced pressure

Sources & evidence

ORD record
ord-7b33e4a99a72447f871a52c0796ab739
Source dataset
uspto-grants-1989_09
Patent number
US04867913

Reaction notes

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