Hydrochloric Acid → HCID 45141331, compound

HRID 1501289Notes

Reaction equation

HRID 1501289 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[CH2:6][NH:7][CH2:8][CH:9](OC)OC.CO/N=[CH:22]/[C:23]1[CH:31]=[CH:30][C:26]2[O:27][CH2:28][O:29][C:25]=2[C:24]=1[CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.Cl.[NH4+].[OH-]>O>[CH3:18][O:17][C:16]1[CH:15]=[C:14]2[C:5](=[CH:4][C:3]=1[O:2][CH3:1])[CH:6]=[N:7][C:8]1[C:31]3[CH:30]=[C:26]4[O:27][CH2:28][O:29][C:25]4=[C:24]([CH2:32][N:33]4[CH2:34][CH2:35][CH2:36][CH2:37]4)[C:23]=3[CH2:22][C:9]2=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 12378777HCID 12378777, compoundHCID 45141116HCID 45141116, compound

Product 1

HCID 45141331HCID 45141331, compoundYield 6.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

The amine 8 (1.90 g, 7.45 mmol) and oxime ether 13b (0.90 g, 3.44 mmol) were mixed with concentrated hydrochloric acid (15 mL) and the mixture was stirred at 100° C. for 18 h. The reaction mixture was then cooled and washed with ether (3×20 mL). It was then brought to basic pH with NH4OH. The mixture was extracted with chloroform (40 mL×3), and the solution was washed with brine (50 mL), dried (Na2SO4) and concentrated. The residue was dissolved in chloroform (40 mL) and filtered. Hydrochloric acid (2 M HCl in ether, 5 mL) was added to the filtrate. The precipitate that formed was recrystallized from methanol to provide a yellow solid. The solid was dissolved in water, basified with NH4OH and extracted with chloroform. The organic layer was concentrated to dryness. The residue was purified by preparative flash chromatography (SiO2, methanol-chloroform-TEA=3:97:2) to yield the final pure product 14b as a light yellow solid (84.9 mg, 6.1%): mp 210° C. (dec). IR (KBr) 2958, 1449, 1406, 1326, 1246 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.94 (s, 1H), 7.44 (s, 1H), 7.16 (s, 1H), 7.01 (s, 1H), 6.04 (s, 2H), 4.07 (s, 3H), 4.02 (s, 3H), 3.85 (s, 2H), 3.79 (s, 2H), 2.67 (broad s, 4H), 1.82 (broad s, 4H); low resolution ESIMS m/z (rel intensity) 405 (MH+, 15), 334 (100). Anal. (C24H24N2O4.1.75H2O) C, H, N.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. washwashed with ether (3×20 mL)
  3. extractionThe mixture was extracted with chloroform (40 mL×3)
  4. washthe solution was washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in chloroform (40 mL)
  8. filtrationfiltered
  9. additionHydrochloric acid (2 M HCl in ether, 5 mL) was added to the filtrate
  10. customThe precipitate that formed
  11. customwas recrystallized from methanol
  12. customto provide a yellow solid
  13. extractionextracted with chloroform
  14. concentrationThe organic layer was concentrated to dryness
  15. customThe residue was purified by preparative flash chromatography (SiO2, methanol-chloroform-TEA=3:97:2)

Sources & evidence

ORD record
ord-bddda196112d4208a2ce3df518346274
Source dataset
uspto-grants-2015_12
Patent number
US09206193B2

Reaction notes

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