Pyridine → HCID 24277619, compound

HRID 1908698Notes

Reaction equation

HRID 1908698 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:16](=[CH:17][CH:18]=1)[O:15][C:9]1([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:8][C:7]2=O)[CH3:2].Cl.O([NH2:23])C.N1C=CC=CC=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CO.O1CCCC1.CCOCC>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:16](=[CH:17][CH:18]=1)[O:15][C:9]1([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:8][CH:7]2[NH2:23])[CH3:2]

Participants

8

Reactant 4

HCID 1049PyridineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 21226445Aluminium lithium hydrideHCID 69012639HCID 69012639, compound

Product 1

HCID 24277619HCID 24277619, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of Example 10A (1.182 g, 4.55 mmol), methoxylamine hydrochloride (380 mg, 4.55 mmol), and pyridine (1.8 mL, 22.3 mmol) in methanol (15 mL) was stirred overnight at room temperature. After this time, the solvent was evaporated in vacuo, then the residue was dissolved in ether and washed with water and brine. The organic layer was dried (Na2SO4), filtered and was evaporated in vacuo, and the residue was further dried azeotropically (CH3CN). A solution of the residue (942 mg, 3.26 mmol) in tetrahydrofuran (10 mL) was treated slowly with 1M LiAlH4 in tetrahydrofuran (5 mL, 5 mmol). After the addition was complete, the reaction was refluxed for 2.5 h. The mixture was cooled to room temperature and carefully quenched with water and was then filtered. The filter pad was washed with ethyl acetate, and the combined filtrates were evaporated in vacuo to afford a gold oil. This was taken up in ether and extracted with 1N HCl, then the acidic extracts were basified with 2N NaOH and were extracted with ethyl acetate. Drying of the organic extracts (Na2SO4), filtered, followed by evaporation in vacuo, afforded the title compound as a gold oil, 320 mg (38%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.10 (d, J=2.7 Hz, 1H), 6.58-6.66 (m, 2H), 3.93 (q, J=7.1 Hz, 2H), 3.78 (m, 1H), 2.04 (m, 1H), 1.36-1.77 (m, 11H), 1.17 (t, J=7.0 Hz, 3H). MS (DCI+) m/z 262 (M+H).

Workup

  1. customAfter this time, the solvent was evaporated in vacuo
  2. dissolutionthe residue was dissolved in ether
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customwas evaporated in vacuo
  7. dry with materialthe residue was further dried azeotropically (CH3CN)
  8. additionAfter the addition
  9. temperaturethe reaction was refluxed for 2.5 h
  10. customcarefully quenched with water
  11. filtrationwas then filtered
  12. washThe filter pad was washed with ethyl acetate
  13. customthe combined filtrates were evaporated in vacuo
  14. customto afford a gold oil
  15. extractionextracted with 1N HCl
  16. extractionwere extracted with ethyl acetate
  17. dry with materialDrying of the organic extracts (Na2SO4)
  18. filtrationfiltered
  19. customfollowed by evaporation in vacuo

Sources & evidence

ORD record
ord-105db5aaf31a477b94bc365ae287a36a
Source dataset
uspto-grants-2013_12
Patent number
US08598220B2

Reaction notes

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