Tetrahydrofuran → 21-Acetoxy-6-chloro-11beta-hydroxy-16alpha-methyl-1,4,6-pregnatriene-3,20-dione

HRID 2049151Notes

Reaction equation

HRID 2049151 reaction equation
[C:1]([O:4][CH2:5][C:6](=[O:30])[C@@H:7]1[C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@H:21]([C@@H:22]([OH:26])[CH2:23]2)[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:27])[CH2:17][CH2:18]2)[C:13]([Cl:28])=[CH:12]3)[CH2:9][C@H:8]1[CH3:29])(=[O:3])[CH3:2].O1CCCC1.Br.[NH+]1C=CC=CC=1>CC(C)=O>[C:1]([O:4][CH2:5][C:6](=[O:30])[C@@H:7]1[C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@H:21]([C@@H:22]([OH:26])[CH2:23]2)[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:27])[CH:17]=[CH:18]2)[C:13]([Cl:28])=[CH:12]3)[CH2:9][C@H:8]1[CH3:29])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 21226041Pyridinium hydrobromideHCID 7058539321-Acetoxy-6-chloro-11beta-hydroxy-16alpha-methyl-4,6-pregnadiene-3,20-dione

Product 1

HCID 7058383021-Acetoxy-6-chloro-11beta-hydroxy-16alpha-methyl-1,4,6-pregnatriene-3,20-dione

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 10.45 g. of 21-acetoxy-6-chloro-11β-hydroxy-16α-methyl-4,6-pregnadiene-3,20-dione in 80 ml. of tetrahydrofuran is combined with 6.5 g. of pyridinium hydrobromide perbromide in 26 ml. of tetrahydrofuran and agitated for 20 minutes at 25°. Subsequently, 0.6 ml. of acetone is added thereto and the mixture is filtered. The filtrate is concentrated under vacuum to a volume of 10 ml., and combined with 80 ml. of dimethylformamide, 4.5 g. of lithium carbonate, as well as 1.62 g. of lithium bromide. The mixture is heated for 2.5 hours to 105° and concentrated under vacuum at 60° to a volume of 40 ml. The mixture is combined with 10 ml. of acetic acid and 14 ml. of water and stirred into 350 ml. of ice water. The thus-obtained precipitate is filtered off, washed with water, and dried in the air. The crude product, 9.4 g., is chromatographed on silica gel. With 40% ethyl acetate-hexane and after recrystallization from acetone-diisopropyl ether, 1.81 g. of 21-acetoxy-6-chloro-11β-hydroxy-16α-methyl-1,4,6-pregnatriene-3,20-dione is obtained, m.p. 192° [α]D25 =+136° (pyridine). UV: ε228 =11,100, ε256 =10,500, ε299 =9,800 (methanol).

Workup

  1. filtrationthe mixture is filtered
  2. concentrationThe filtrate is concentrated under vacuum to a volume of 10 ml
  3. temperatureThe mixture is heated for 2.5 hours to 105°
  4. concentrationconcentrated under vacuum at 60° to a volume of 40 ml
  5. filtrationThe thus-obtained precipitate is filtered off
  6. washwashed with water
  7. customdried in the air
  8. custom, is chromatographed on silica gel
  9. customWith 40% ethyl acetate-hexane and after recrystallization from acetone-diisopropyl ether, 1.81 g

Sources & evidence

ORD record
ord-01c499bd9a77468f9d5b749158eb842d
Source dataset
uspto-grants-1980_04
Patent number
US04196203

Reaction notes

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