Ammonium Chloride → HCID 178441684, compound

HRID 975284Notes

Reaction equation

HRID 975284 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]#[N:27])=[CH:16][CH:15]=2)[C:7]([CH2:11][OH:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].[N-:28]=[N+:29]=[N-:30].[Na+].[Cl-].[NH4+]>CN(C=O)C>[CH2:1]([C:5]1[N:6]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3[NH:30][N:29]=[N:28][N:27]=3)=[CH:18][CH:19]=2)[C:7]([CH2:11][OH:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 25517Ammonium Chloride2×HCID 33557Sodium Azide2×HCID 144256644'-((2-Butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

Product 1

HCID 178441684HCID 178441684, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imidazole (11.93 g, 1.0 eq), sodium azide (3 eq), and ammonium chloride (3 eq) were mixed and stirred in DMF (150 mL) in a round bottom connected to a reflux condenser under N2. An oil bath with a temperature controller was then used to heat the reaction at 100° C. for 2 days, after which the temperature was raised to 120° C., for 6 days. The reaction was cooled and 3 more equivalents of ammonium chloride and sodium azide were added. The reaction was again heated for 5 more days at 120° C. The reaction was cooled, the inorganic salts filtered, and the filtrate solvent removed in vacuo. Water (200 mL) and ethyl acetate (200 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×200 mL), the organic layers were collected, dried (MgSO4) and the solvent removed in vacuo, to yield a dark yellow oil. The product was purified by flash chromatography in 100% ethyl acetate to 100% ethanol over silica gel to yield 5.60 g of a light yellow solid. Recrystallization from acetonitrile yielded 4.36 g of light yellow crystals which still melted broadly. The crystals were taken up in 100 mL of hot acetonitrile. The solid that did not dissolve was filtered off to yield 1.04 g of product as a light yellow solid; m.p. 183.5°-184.5°. Upon cooling, the mother liquor yielded an additional 1.03 g of product as a light yellow solid; m.p. 179.0°-180.0°. NMR (200 MHz, DMSO-d6)δ7.75-7.48 (m, 4H); 7.07 (d, 2H, J=9 Hz); 7.04 (d, 2H, J=9 Hz); 5.24 (s, 2H); 5.24 (bs, 1H); 4.34 (s, 2H); 2.48 (t, 2H, J=7 Hz); 1.48 (t of t, 2H, J=7,7 Hz); 1.27 (t of q, 2H, J=7,7 Hz); 0.81 (t, 3H, J=7 Hz).

Workup

  1. custombottom connected to a reflux condenser under N2
  2. customAn oil bath with a temperature controller was then used
  3. temperatureto heat
  4. customthe reaction at 100° C. for 2 days
  5. temperatureThe reaction was cooled
  6. temperatureThe reaction was again heated for 5 more days at 120° C
  7. temperatureThe reaction was cooled
  8. filtrationthe inorganic salts filtered
  9. customthe filtrate solvent removed in vacuo
  10. additionWater (200 mL) and ethyl acetate (200 mL) were added to the residue
  11. customthe layers were separated
  12. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
  13. customthe organic layers were collected
  14. dry with materialdried (MgSO4)
  15. customthe solvent removed in vacuo
  16. customto yield a dark yellow oil
  17. customThe product was purified by flash chromatography in 100% ethyl acetate to 100% ethanol over silica gel

Sources & evidence

ORD record
ord-e28fdbf7293b4747ba0d63e6293d259b
Source dataset
uspto-grants-1997_03
Patent number
US05608075

Reaction notes

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