Methanol → Androsta-4,16-dien-3-one

HRID 1738775Notes

Reaction equation

HRID 1738775 reaction equation
[CH3:1][C@@:2]12[C@@H:10](O)[CH2:9][CH2:8][C@H:7]1[C@@H:6]1[CH2:12][CH2:13][C:14]3[C@@:20]([CH3:21])([C@H:5]1[CH2:4][CH2:3]2)[CH2:19][CH2:18][C:16](=[O:17])[CH:15]=3.ClC(OC)=O.N1C=CC=CC=1.CO.C(=O)([O-])OC>C1(C)C=CC=CC=1>[CH3:1][C@:2]12[CH2:3][CH2:4][C@H:5]3[C@@H:6]([CH2:12][CH2:13][C:14]4[C@:20]3([CH3:21])[CH2:19][CH2:18][C:16](=[O:17])[CH:15]=4)[C@@H:7]1[CH2:8][CH:9]=[CH:10]2

Participants

6

Reactant 4

HCID 887MethanolHCID 6013TestosteroneHCID 4585885MethylcarbonateHCID 86585582Methyl chloroformate pyridine

Product 1

HCID 92979Androsta-4,16-dien-3-oneYield 90%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

This synthesis is depicted in FIG. 1. Several methods are known for the conversion of testosterone into Androsta-4,16-dien-3-one (Brooksbank et al, Biochem. J. (1950) AZ:36). Alternatively, thermolysis (460°) of the methyl carbonate of testosterone gives Androsta-4,16-dien-3-one in 90% yield. 17B-MethoxyCarbonyioxy-androst-4-en-3-one (IV) was prepared from testosterone (III. Fluka) with methyl chloroformate/pyridine (a) in 76% yield (after recrystallization from MeOH). M.p. 140-141°, [a]D =+95.4°(c=1.10) IR. (CDCl3):1740s, 1665s, 1450s, 1280s , 1H-NMR. (360 MHz):0.87 (s, 3H); 1.20 (s, 3H); 3.77 (s, 3H); 4.53 (br. t, J 8, 1H); 5.75 (s, 1H). A solution of the methyl carbonate IV in toluene was pyrolyzed (b) as described for I. Recrystallization of the crude product from acetone at RT. gave pure ketone 4 in 90% yield. M.p. 127-129.5°, (a)D +118.90°(C=1.32) ([3]:m.p. 131.5-133.5°(hexane), [a]D16 =+123±3.50°(C=1.03)). IR. (CDCl3):3050w, 1660s, 1615m. 1H-NMR. (360 MHz):0.82 (s, 3H); 1.22 (s, 3H); 5.70 (m, 1H); 5.73 (s, 1H); 5.84 (m, 1H).

Workup

  1. customM.p. 140-141°, [a]D =+95.4°(c=1.10) IR
  2. customRecrystallization of the crude product from acetone at RT

Sources & evidence

ORD record
ord-5b5dcee507c84ab3aa2d77bce0a2bbb1
Source dataset
uspto-grants-1999_10
Patent number
US05965552

Reaction notes

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