Acetic Acid → HCID 10981608, compound

HRID 1738815Notes

Reaction equation

HRID 1738815 reaction equation
CC(C)([O-])C.[K+].[CH:7]1([O:10][C@H:11]2[CH2:16][CH2:15][C@H:14]3[C@H:17]4[C@H:27]([CH2:28][CH2:29][C@:12]23[CH3:13])[C@:25]2([CH3:26])[C:20](=[CH:21][C:22](=[O:30])[CH2:23][CH2:24]2)[CH2:19][CH2:18]4)[CH2:9][CH2:8]1.C([O:34][N+:35]([O-])=[O:36])(C)C.C(O)(=O)C>C(O)(C)(C)C.[Cl-].[Na+].O.C(Cl)Cl>[CH:7]1([O:10][C@H:11]2[CH2:16][CH2:15][C@H:14]3[C@H:17]4[C@H:27]([CH2:28][CH2:29][C@:12]23[CH3:13])[C@:25]2([CH3:26])[C:20](=[C:21]([N+:35]([O-:36])=[O:34])[C:22](=[O:30])[CH2:23][CH2:24]2)[CH2:19][CH2:18]4)[CH2:8][CH2:9]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 15575Isopropyl nitrateHCID 10640035HCID 10640035, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 10981608HCID 10981608, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

Potassium tert-butoxide (109 g, 0.97 mol, 2.1 molar equivalents) is added to a stirred solution of 17β-(cyclopropyloxy)-androst-4-en-3-one (150 g, 0.46 mol) in tert-butanol (2 L) over 10 minutes at room temperature and under nitrogen. Continue stirring at room temperature for 18 hours, then add isopropylnitrate (48.2 g, 0.46 mol, 1.0 mol. equiv.) in tert-butanol (50 mL) over 30 minutes at room temperature. After an additional day of continuous stirring at room temperature, glacial acetic acid (130 mL) is added over 25 minutes and stirring is continued for an additional 18 hours. Subsequently, methylene chloride (1.5 L) and brine (saturated NaCl, 800 mL) is added and the solution is stirred an additional 10 minutes. The organic phase is then seperated and dried over magnesium sulfate. The resulting slurry is filered and the filtrate concentrated (35° C./40 Torr) to give a dark red oil. Purify by flash chromatography (SiO2, elution: EtOAc/hexane 5:95, EtOAc/hexane 1:9 and EtOAc/hexane 15:85). Combine and concentrate the fractions containing the desired product (30° C./40 Torr) to give a solid residue which is stirred under hexane (350 mL). Filter and dry the solids to give the title compound (68 g, 40%) as a yellow solid. Additional compound is obtained from the filtrate after concentration and rechromatography as above (8 g, 5%). mp 133-134° C.

Workup

  1. stirringAfter an additional day of continuous stirring at room temperature
  2. stirringstirring
  3. waitis continued for an additional 18 hours
  4. stirringthe solution is stirred an additional 10 minutes
  5. customThe organic phase is then seperated
  6. dry with materialdried over magnesium sulfate
  7. concentrationthe filtrate concentrated (35° C./40 Torr)
  8. customto give a dark red oil
  9. customPurify by flash chromatography (SiO2, elution: EtOAc/hexane 5:95, EtOAc/hexane 1:9 and EtOAc/hexane 15:85)
  10. concentrationCombine and concentrate the fractions
  11. additioncontaining the desired product (30° C./40 Torr)
  12. customto give a solid residue which
  13. stirringis stirred under hexane (350 mL)
  14. filtrationFilter
  15. customdry the solids

Sources & evidence

ORD record
ord-2872c97ce6914e098690890ee06e5c04
Source dataset
uspto-grants-1999_10
Patent number
US05965550

Reaction notes

Loading…