Toluene → 17-(1H-benzimidazol-1-yl)androsta-4,16-diene-3-one

HRID 254186Notes

Reaction equation

HRID 254186 reaction equation
[OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C:4](=[CH:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[CH2:9][CH:10]=[C:11]2[N:21]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[N:23]=[CH:22]2)[CH2:3]1.CN1CCC(=O)CC1.C1(C)C=CC=CC=1.CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-]>CCOC(C)=O>[N:21]1([C:11]2[C@:12]3([CH2:14][CH2:15][C@H:16]4[C@@H:7]([CH2:6][CH2:5][C:4]5[C@:17]4([CH3:20])[CH2:18][CH2:19][C:2](=[O:1])[CH:3]=5)[C@@H:8]3[CH2:9][CH:10]=2)[CH3:13])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=[CH:22]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 11143Aluminum isopropoxideHCID 740491-Methyl-4-piperidoneHCID 11188409Galeterone

Product 1

HCID 1122291717-(1H-benzimidazol-1-yl)androsta-4,16-diene-3-oneYield 82.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

From a mixture of compound 5 (660 mg, 1.70 mmol), 1-methyl-4-piperidone (2.5 mL), and toluene (40 mL) was distilled off ca. 10 mL. Aluminum isopropoxide (521 mg, 2.55 mmol) was then added, and the mixture was refluxed under Ar for 4 h. After cooling, the mixture was diluted with EtOAc (50 mL), washed successively with 5% aqueous NaHCO3 (x3) and brine (x2), and then dried (Na2SO4). The solvent was evaporated, and the crude product was purified by FCC [CH2Cl2/EtOH (25:1)] to give the title compound 6 (544 mg, 82%): mp 201-204° C.; IR(CHCl3) 2946, 2858, 1622, 1611, 1490, 1453, 1376, 1291, 1270, 1228, 1189, 893, 850, 837, 722, 662, 615, 568, 553, 537, 519 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.04 (s, 3H 18-CH3), 1.24 (s, 3H, 19-CH3), 5.78 (s, 1H, 4-H), 5.99 (s, 1H, 16-H), 7.31 (m, 2H, aromatic-Hs), 7.48 (m, 1H, aromatic-H), 7.81 (s, 1H, aromatic-H), and 7.95 (s, 1H, 21-H). HRMS calcd 409.2250 (C26H30ON2.Na+). found 409.2250.

Workup

  1. distillationwas distilled off ca. 10 mL
  2. temperaturethe mixture was refluxed under Ar for 4 h
  3. temperatureAfter cooling
  4. washwashed successively with 5% aqueous NaHCO3 (x3) and brine (x2)
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was evaporated
  7. customthe crude product was purified by FCC [CH2Cl2/EtOH (25:1)]

Sources & evidence

ORD record
ord-2b5ee5624abf4935b8a5eacd0b73b184
Source dataset
uspto-grants-2011_01
Patent number
US07875599B2

Reaction notes

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