Cyclohexanone → 4-Androstene-17-carboxylic acid, 3-oxo-, methyl ester

HRID 354912

반응식

HRID 354912 반응식
C[C:2]([C@@H:4]1[C@@:8]2([CH3:23])[CH2:9][CH2:10][C@@H:11]3[C@@:16]4([CH3:22])[CH2:17][CH2:18][C@H:19]([OH:21])[CH2:20][C:15]4=[CH:14][CH2:13][C@H:12]3[C@@H:7]2[CH2:6][CH2:5]1)=[O:3].[CH3:24][O-:25].[Na+].CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].C1(=O)CCCCC1>C1(C)C=CC=CC=1.CO>[CH3:24][O:25][C:2]([CH:4]1[CH2:5][CH2:6][C@H:7]2[C@H:12]3[C@H:11]([CH2:10][CH2:9][C@:8]12[CH3:23])[C@:16]1([CH3:22])[C:15](=[CH:20][C:19](=[O:21])[CH2:18][CH2:17]1)[CH2:14][CH2:13]3)=[O:3]

참가 물질

7

반응물 4

HCID 7967CyclohexanoneHCID 8955PregnenoloneHCID 11143Aluminum isopropoxideHCID 10942334Sodium Methoxide

생성물 1

HCID 228121484-Androstene-17-carboxylic acid, 3-oxo-, methyl ester

시약·촉매·용매 2

HCID 887Methanol용매HCID 1140Toluene용매

실험 절차

A preferred process for preparing 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one, an especially preferred compound of the present invention, comprises the following steps: (a) pregnenolone (V), an available starting material, is treated by the haloform King reaction with iodine and pyridine to form the 20-pyridinum iodide derivative of the pregnenolone (VI); (b) the pyridinium iodide derivative (VI) is hydrolyzed to the methyl ester of 17-carboxy pregnenolone (VII) with sodium methoxide and methanol, the ester form being preferred for carrying out the following Oppenhauer reaction; (c) the methyl ester of 17-carboxy pregnenolone (VII) is treated with aluminum isopropoxide and cyclohexanone in an appropriate solvent such as toluene to yield methyl-4-androstene-3-one-17-carboxylate (VIII) (d) the methyl-4-androstene-3-one-17-carboxylate (VIII) thus formed is hydrolyzed to the 17-acid (IX) under acid conditions in a methanol: water solvent of approximately 4:1 proportions; (e) the 17 acid (IX) is then treated with an oxalyl chloride: pyridine complex of approximately 1:1 proportions in toluene or other suitable solvent, e.g. xylene, to form the 17-acid chloride (X); (f) the 17-acid chloride (X) is then treated in situ with an excess of diethylamine to form the 17β-N,N-diethylcarbamoyl-4-androstene-3-one (XI); (g) the 4-androstene-3-one (XI) thus formed is oxidized by treatment with sodium periodate and potassium permanganate, using tert-butanol and water as a solvent system, to the corresponding 5-oxo-3,5-secoandrostan-3-oic acid (XII); (h) the secoandrostanoic acid (XII) is then converted to the corresponding 4-aza compound (XIII) by treating it with methylamine in ethylene glycol for a period of about 1 hour over which time the reaction mixture temperature is raised to from 140°-180° C. where it is maintained from 0.5 to 5 minutes; (i) the resulting 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androsten-3-one (XIII) is then hydrogenated by treating it with hydrogen at room temperature to 60° C. or higher, using platinum oxide as the catalyst, to form the 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one (XIV) final product, which is then separated and purified.

후처리

  1. customthe following Oppenhauer reaction

출처 및 근거

ORD 기록
ord-f73f569ea3894c74a4c6f285cde09426
출처 데이터셋
uspto-grants-1983_03
특허 번호
US04377584

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