Ammonium Hydroxide → HCID 45141333, compound

HRID 1501291Notes

Reaction equation

HRID 1501291 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.CON=[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[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]1.[NH4+].[OH-]>Cl>[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][N:36]([CH3:39])[CH2:37][CH2:38]4)[C:23]=3[CH2:22][C:9]2=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 12378777HCID 12378777, compoundHCID 75097399HCID 75097399, compound

Product 1

HCID 45141333HCID 45141333, compoundYield 3.5%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
100 °C

Procedure

The amine 8 (560.3 mg, 2.19 mmol) and oxime ether 13d (320.2 mg, 1.10 mmol) were mixed together with concentrated hydrochloric acid (10 mL) and the mixture was stirred at 100° C. for 3 h. The reaction mixture was then cooled and washed with ether (3×20 mL). It was then brought to basic pH with 28% aqueous NH4OH. The mixture was extracted with CHCl3 (3×40 mL), and the organic layer was washed with brine (50 mL), dried with anhydrous Na2SO4 and concentrated. The residue was diluted in CHCl3 (40 mL) and filtered. Hydrochloric acid (2 M HCl in ether, 10 mL) was added to the filtrate. A dark yellow precipitate was obtained and recrystallized from methanol to provide a bright yellow solid. NH4OH (2 mL) was added to the yellow solid and the mixture was concentrated to dryness. The residue was purified by preparative flash chromatography (SiO2, methanol-chloroform-TEA=10:90:2) to yield the final pure product 14d as a yellow solid (16.7 mg, 3.5%): mp 296° C. (dec). IR 3400, 1489, 1455, 1245, 1159 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.98 (s, 1H), 7.47 (s, 1H), 7.24 (s, 1H), 7.08 (s, 1H), 6.04 (s, 2H), 4.11 (s, 3H), 4.04 (s, 3H), 3.91 (s, 2H), 3.68 (s, 2H), 2.65 (brs, 4H), 2.56 (brs, 4H), 2.34 (s, 3H); ESIMS m/z (rel intensity) 434 (MH+, 100), 334 (25). Anal. (C25H27N3O4.3.5H2O) C, H, N.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. washwashed with ether (3×20 mL)
  3. extractionThe mixture was extracted with CHCl3 (3×40 mL)
  4. washthe organic layer was washed with brine (50 mL)
  5. dry with materialdried with anhydrous Na2SO4
  6. concentrationconcentrated
  7. additionThe residue was diluted in CHCl3 (40 mL)
  8. filtrationfiltered
  9. additionHydrochloric acid (2 M HCl in ether, 10 mL) was added to the filtrate
  10. customA dark yellow precipitate was obtained
  11. customrecrystallized from methanol
  12. customto provide a bright yellow solid
  13. concentrationthe mixture was concentrated to dryness
  14. customThe residue was purified by preparative flash chromatography (SiO2, methanol-chloroform-TEA=10:90:2)

Sources & evidence

ORD record
ord-422a38ac569b47cd8a66fbb84d57b27d
Source dataset
uspto-grants-2015_12
Patent number
US09206193B2

Reaction notes

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