Hydroxyamine hydrochloride → 3beta,16beta-Dimethylandrost-5-en-17-one

HRID 2393211Notes

Reaction equation

HRID 2393211 reaction equation
CC(C)=[O:3].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:16][C@H:17]1[CH2:36][CH2:35][C@@:34]2([CH3:37])[C:19](=[CH:20][CH2:21][C@@H:22]3[C@@H:33]2[CH2:32][CH2:31][C@@:30]2([CH3:38])[C@H:23]3[CH2:24][C:25]([CH3:39])=[C:26]2C(=O)C)[CH2:18]1.Cl.NO.C(NC1C=CC(S(Cl)(=O)=O)=CC=1)(=O)C.N1C=CC=CC=1.C(NC1[C@]2(CC[C@H]3[C@@H](CC=C4[C@]3(C)CC[C@H](C)C4)[C@@H]2CC=1C)C)(=O)C>C(O)C.O1CCCC1.Cl.N1C=CC=CC=1>[CH3:16][C@H:17]1[CH2:36][CH2:35][C@@:34]2([CH3:37])[C:19](=[CH:20][CH2:21][C@@H:22]3[C@@H:33]2[CH2:32][CH2:31][C@@:30]2([CH3:38])[C@H:23]3[CH2:24][C@H:25]([CH3:39])[C:26]2=[O:3])[CH2:18]1

Participants

9

Reactant 5

HCID 443297Hydroxyamine hydrochlorideHCID 186376553beta,16-Dimethyl,5,16-pregnadien-20-oneHCID 18978461Acetone p-toluenesulfonic acidHCID 5720142817-Acetamido-3beta,16-dimethyl-5,16-androstadieneHCID 88342963p-Acetamidobenzenesulfonyl chloride pyridine

Product 1

HCID 186376543beta,16beta-Dimethylandrost-5-en-17-one

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1049PyridineSolventHCID 18422008HCl tetrahydrofuranSolvent

Procedure

To a solution of 16β-methyl-3β-hydroxy-5,16-pregnadien-20-one was added toluene, ethylene glycol, and p-toluene-sulfonic acid. The resulting solution was refluxed overnight forming the 20-ketal. The procedure for this ketalization step is described in JACS, 76, 5674 (1954). Tosyl chloride in pyridine was added to the above product to form the 3β-tosylate derivative. The 3β-tosylate was refluxed overnight with 10% NaI/acetone to form the 3β-iodo-16-methyl-5,16-pregnadien-20-one-ethylene ketal. This product was methylated with lithium dimethylcuprate in ether and tetrahydrofuran at -78° C. under a nitrogen atmosphere to form the 3β,16-dimethyl-5,16-pregnadien-20-one ethylene ketal. This product was deketalized by refluxing in the presence of acetone/p-toluenesulfonic acid. The resulting 3β,16-dimethyl,5,16-pregnadien-20-one was converted to the C-20-oxime by refluxing in ethanol and pyridine with an excess of hydroxylamine hydrochloride. This product was subjected to a Beckmann rearrangement in the presence of p-acetamidobenzenesulfonyl chloride/pyridine according to the procedure by Rosenkranz, et al. in J. Org. Chem., 21, 520-522 (1956). The product, 17-acetamido-3β,16-dimethyl-5,16-androstadiene was refluxed in tetrahydrofuran/hydrochloric acid solution. 3β,16β-dimethyl-5-androst-en-17-one was formed, separated and purified by normal phase HPLC using a 1 in.×25 cm silica gel preparative column at a flow rate of 30 ml/min and using ethyl acetate/hexane (in a gradient ranging from 0 to 20%) as the eluent. The product was recrystallized from methanol and characterized by NMR and IR. Colorless crystals were isolated: 3β,16β-dimethyl-5-androsten-17-one m.p. 86.5°-88.5° C.

Sources & evidence

ORD record
ord-c083db8fbd3541998bd784207faffc4b
Source dataset
uspto-grants-1998_09
Patent number
US05804576

Reaction notes

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