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

HRID 59056Notes

Reaction equation

HRID 59056 reaction equation
[N:1]1([C:10]2[C@:11]3([CH2:28][CH2:27][C@H:26]4[C@@H:16]([CH2:17][CH2:18][C:19]5[C@:24]4([CH3:25])[CH2:23][CH2:22][C:21](=[O:29])[CH:20]=5)[C@@H:13]3[CH2:14][CH:15]=2)[CH3:12])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Li][CH3:31]>C1COCC1>[CH3:31][C:21]1([OH:29])[CH2:22][CH2:23][C@@:24]2([CH3:25])[C:19]([CH2:18][CH2:17][C@@H:16]3[C@@H:26]2[CH2:27][CH2:28][C@@:11]2([CH3:12])[C@H:13]3[CH2:14][CH:15]=[C:10]2[N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)=[CH:20]1

Participants

4

Reactant 2

HCID 1122291717-(1H-benzimidazol-1-yl)androsta-4,16-diene-3-oneHCID 178418348HCID 178418348, compound

Product 1

HCID 717349203-Methyl-3-hydroxy-17-(1H-benzimidazol-1-yl)-androsta-4,16-dieneYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ketone (32) (0.1 g, 0.26 mmol) in dry THF (3 mL) was added MeLi (1.6 M solution in ether, 0.41 mL, 0.60 mmol) at −60° C., and the resulting mixture was stirred at 0° C. for 1 h then room temperature for 3 h. The reaction was quenched with saturated aqueous NH4Cl and was extracted with EtOAc. The organic layer was washed with brine and dried over Na2SO4, and the solvent was removed under vacuum. The residue was purified by short FCC [petroleum ether, EtOAc, TEA (60:40:0.5)] to afford product 40 (0.05 g, 48%); mp 95-97° C.; IR (Neat) 3329, 2827, 2853, 1489, 1453, 1376, 1292, 1226, 1133, 918, 741 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.00 (s, 3H, 18-CH3), 1.07 (s, 3H, 19-CH3), 1.27 (s, 3H, C3-CH3), 5.25 (t, J=1.6 Hz, 1H, 6-H), 5.96 (t, 1H, J=1.52 Hz, 16-H), 7.29 (m, 2H, aromatic-Hs), 7.49 (m, 1H, aromatic-H), 7.82 (dd, J=7.0, 2.6 Hz, 1H, aromatic-H), and 7.95 (s, 1H, 2′-H); 13C NMR (500 MHz, CDCl3) δ 145.3, 127.6, 124.4, 123.6, 122.7, 120.4, 111.4, 70.1, 55.7, 54.8, 37.8, 35.6, 35.3, 34.7, 32.5, 30.4, 28.5, 21.1, 18.8, 16.3. HRMS calcd 425.2563 (C27H34ON2.Na+). found 425.2570.

Workup

  1. waitroom temperature for 3 h
  2. customThe reaction was quenched with saturated aqueous NH4Cl
  3. extractionwas extracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed under vacuum
  7. customThe residue was purified by short FCC [petroleum ether, EtOAc, TEA (60:40:0.5)]

Sources & evidence

ORD record
ord-e6a1ab2a38ec428cb785be350c427a27
Source dataset
uspto-grants-2016_09
Patent number
US09439912B2

Reaction notes

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