Pyridine → HCID 24277618, compound

HRID 1908697Notes

Reaction equation

HRID 1908697 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[C:15]([Cl:17])[CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[CH2:6][C:5]2=O.Cl.O([NH2:22])C.N1C=CC=CC=1.[OH-].[K+]>CO.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[C:15]([Cl:17])[CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[CH2:6][CH:5]2[NH2:22]

Participants

7

Reactant 4

HCID 1049PyridineHCID 14797Potassium HydroxideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 12462881HCID 12462881, compound

Product 1

HCID 24277618HCID 24277618, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of Example 6A (1.001 g, 3.51 mmol), methoxylamine hydrochloride (293 mg, 3.51 mmol), and pyridine (1.4 mL, 17.3 mmol) in methanol (25 mL) was stirred overnight at room temperature. After this time, the solvent was evaporated in vacuo, and the residue was dissolved in ether and washed with water and brine. The organic layer was dried (Na2SO4), filtered and evaporated in vacuo, and the residue further dried azeotropically (CH3CN). A solution of the residue in tetrahydrofuran (4 mL) was cooled to 0° and was then treated slowly with 1M BH3-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 was treated carefully with H2O (3 mL) and 20% aq. KOH (3 mL), then was refluxed for 1 h. The mixture was cooled and extracted with ethyl acetate. The organic extracts were washed with 1N HCl. The aqueous layer was basified with 2M NaOH, followed by extraction with ethyl acetate, afforded the title compound as a yellow oil, 64 mg (6%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.55 (dd; J=14.9, 2.7 Hz; 1H), 7.36 (m, 1H), 3.82 (m, 1H), 2.11 (m, 2H), 1.20-1.82 (m, 10H). MS (DCI+) m/z 286 (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. customevaporated in vacuo
  7. dry with materialthe residue further dried azeotropically (CH3CN)
  8. temperatureA solution of the residue in tetrahydrofuran (4 mL) was cooled to 0°
  9. additionAfter the addition
  10. temperaturethe reaction was refluxed for 2.5 h
  11. temperaturewas refluxed for 1 h
  12. temperatureThe mixture was cooled
  13. extractionextracted with ethyl acetate
  14. washThe organic extracts were washed with 1N HCl
  15. extractionfollowed by extraction with ethyl acetate

Sources & evidence

ORD record
ord-17019bcefcfb4aeaa3744b8578eefb45
Source dataset
uspto-grants-2013_12
Patent number
US08598220B2

Reaction notes

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