Deoxycorticosterone → 17-(2-((5-Bromopentyl)oxy)acetyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one

HRID 2039394Notes

Reaction equation

HRID 2039394 reaction equation
[CH3:1][C@@:2]12[C@@H:10]([C:11]([CH2:13][OH:14])=[O:12])[CH2:9][CH2:8][C@H:7]1[C@@H:6]1[CH2:15][CH2:16][C:17]3[C@@:23]([CH3:24])([C@H:5]1[CH2:4][CH2:3]2)[CH2:22][CH2:21][C:19](=[O:20])[CH:18]=3.[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]Br.[OH-].[K+].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCl>[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][O:14][CH2:13][C:11]([CH:10]1[C:2]2([CH3:1])[CH:7]([CH:6]3[CH:5]([CH2:4][CH2:3]2)[C:23]2([CH3:24])[C:17](=[CH:18][C:19](=[O:20])[CH2:21][CH2:22]2)[CH2:16][CH2:15]3)[CH2:8][CH2:9]1)=[O:12]

Participants

6

Reactant 4

HCID 6166DeoxycorticosteroneHCID 81001,5-DibromopentaneHCID 14797Potassium HydroxideHCID 2723671Tetrabutylammonium Hydroxide

Product 1

HCID 8667556417-(2-((5-Bromopentyl)oxy)acetyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-oneYield 43.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 21-hydroxyprogesterone (200 mg, 0.605 mmol), 1,5-dibromopentane (1.65 mL, 12.1 mmol), 40% KOH (300 μL), and tetrabutylammonium hydroxide (60 μL) was stirred for 16 h at room temperature. The reaction mixture was diluted in dichloromethane and washed with water three times. The organic layer was dried over sodium sulfate and concentrated by rotary evaporation. The crude residue was purified by flash chromatography with hexanes/ethyl acetate (2:1) as the eluent to afford 7 as a colorless oil (125 mg, 43%). 1H NMR (500 MHz, CDCl3) δ 5.67 (s, 1H), 3.96 (q, J=17.2 Hz, 2H), 3.41 (t, J=6.4 Hz, 2H), 3.38-3.31 (m, 2H), 2.56 (t, J=9.1 Hz, 1H), 2.40-2.09 (m, 6H), 1.96 (m, 1H), 1.90-1.74 (m, 5H), 1.72-1.16 (m, 14H), 1.12 (s, 3H), 1.05-0.86 (m, 2H), 0.65-0.58 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 207.55, 198.50, 169.94, 122.92, 75.79, 70.34, 61.56, 57.43, 55.12, 52.51, 43.53, 37.54, 34.61, 32.85, 31.74, 31.47, 30.82, 28.69, 27.74, 23.77, 23.47, 21.81, 19.97, 16.34, 12.55. ESI-MS m/z [M+H]+ observed: 481.1, calculated: 481.2.

Workup

  1. washwashed with water three times
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated by rotary evaporation
  4. customThe crude residue was purified by flash chromatography with hexanes/ethyl acetate (2:1) as the eluent

Sources & evidence

ORD record
ord-2eb90a60653e4f30baa88e53e86256c1
Source dataset
uspto-grants-2013_11
Patent number
US08580231B2

Reaction notes

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