HCID 12085276, compound → HCID 12085277, compound

HRID 396176Notes

Reaction equation

HRID 396176 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:13]=[CH:14][C:15]([CH2:19][C:20]3[CH:21]=NC=[CH:24][CH:25]=3)=[C:16]([OH:18])[CH:17]=2)=[CH:4][CH:3]=1.CC(C)([O-:29])C.[K+]>C(O)(C)(C)C>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:13]=[CH:14][C:15]([CH2:19][CH:20]3[CH2:25][CH2:24][O:29][CH2:21]3)=[C:16]([OH:18])[CH:17]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 12085276HCID 12085276, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 12085277HCID 12085277, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 200 mg of tert-butyl naphthyl carbamate (Example 6) (0.59 mmol, 1 equiv.) in 1.6 mL anhydrous tert-butanol was added 200 mg of 3-tetrahydrofuroic aldehyde from above (excess) and 1.78 mL potassium tert-butoxide solution in tert-butanol (1.0 M, 1.78 mmol, 3 equiv.). The mixture was heated to 40° C. overnight, then cooled and quenched with NH4Cl saturated aqueous solution. The product was extracted with a dichloromethane/MeOH mixture (3×100 mL). The combined extracts were washed with brine, dried over MgSO4, and concentrated. 1H NMR analysis revealed that only 10% of the enone was consumed. The residue (300 mg) was dissolved in 4.0 mL dichloromethane and treated with 4 mL of a 1:1 mixture dichloromethane:TFA. The mixture was stirred for 1.5 h, then neutralized with saturated NaHCO3 aqueous solution, basified with 4 N NaOH solution and extracted with dichloromethane/MeOH (3×100 mL). The combined organic extracts were washed with brine, dried (MgSO4) and filtered and concentrated. The crude product was purified by column chromatography on silica gel using 10 to 50% EtOAc in hexane eluent mixtures to give the title compound (35 mg 0.11 mmol, 19% of theoretical yield).

Workup

  1. temperaturecooled
  2. customquenched with NH4Cl saturated aqueous solution
  3. extractionThe product was extracted with a dichloromethane/MeOH mixture (3×100 mL)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customwas consumed
  8. dissolutionThe residue (300 mg) was dissolved in 4.0 mL dichloromethane
  9. additiontreated with 4 mL of a 1:1 mixture dichloromethane
  10. extractionextracted with dichloromethane/MeOH (3×100 mL)
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product was purified by column chromatography on silica gel using 10 to 50% EtOAc in hexane eluent mixtures

Sources & evidence

ORD record
ord-cebda6f6650a4f8cb3729cd2fd7bcd62
Source dataset
uspto-grants-2003_08
Patent number
US06608052B2

Reaction notes

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