Hydrochloric Acid → HCID 178423746, compound

HRID 2255528Notes

Reaction equation

HRID 2255528 reaction equation
C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[C:12]([C:13]3[C:18]([C:19]4[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=4)=[CH:17][CH:16]=[C:15]([N+]([O-])=O)[CH:14]=3)=[N:11][N:10]=[N:9]2)C=CC=CC=1.N([O-])=O.[Na+].O.[ClH:46]>CO.CN(C=O)C.S(=O)(=O)(O)O.[Pd].Cl[Cu]>[Cl:46][C:15]1[CH:14]=[C:13]([C:12]2[NH:11][N:10]=[N:9][N:8]=2)[C:18]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)=[CH:17][CH:16]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 23668193Sodium NitriteHCID 131717263HCID 131717263, compound

Product 1

HCID 178423746HCID 178423746, compoundYield 45%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 62652Cuprous chlorideCatalystHCID 1118Sulfuric AcidSolventHCID 21901440N,N-dimethylformamide methanolSolvent

Procedure

A solution of N-triphenylmethyl-5-(4'-methyl-4-nitrobiphen-2-yl)tetrazole (0.115 g, 0.224 mmol) in MeOH/DMF (2 mL/12 mL) was submitted to hydrogenation at 40 psi H2 with 10% Pd on carbon (50 mg) at room temperature for 1 hour. The reaction was filtered through celite and the filtrate was concentrated in vacuo. The triphenyl methyl group had been lost during the hydrogenation. The crude 4-amino compound was dissolved in glacial acetic acid (3 mL) and added slowly to a cooled (0° C.) solution of NaNO2 (28.8 mg, 0.417 mmol) in conc. sulfuric acid (1 mL). The diazonium solution was stirred well for 2 hours then slowly added to a cooled (0° C.) solution of CuCl (0.449 g; 20 equiv) in conc. HCl. This mixture was stirred for 30 minutes and then poured over H2O and extracted with Et2O/EtOAc. The combined organic extracts were washed with H2O and brine, dried over MgSO4 and concentrated in vacuo. The product was purified by flash chromatography on a silica column eluting with Hex/EtOAc/HOAc (80:20;1) to afford 27 mg (45% for 2 steps) of 5-(4-chloro-4'-methyl-biphen-2-yl)tetrazole. The free tetrazole was dissolved in CH2Cl2 (3.5 mL) and NEt3 (0.035 mL, 2.5 equiv) and Ph3CCl (27 mg, 1.0 equiv) were added. After 30 minutes the reaction was diluted with Et2O washed with 10% citric acid, 1N NaOH and brine. The organic was dried over anhydrous MgSO4 and concentrated in vacuo to afford 51.2 mg (100%) of crude N-triphenylmethyl-5-(4-chloro-4'-methyl-biphen-2-yl)tetrazole. 1H NMR (300 MHz, CDCl3) δ 2.26 (s, 3H), 6.91 (d, 6H), 6.94 (ABq, 4H), 7.20-7.25 (comp, 7H), 7.43 (dd, 1H), 7 99 (dd, 1H).

Workup

  1. filtrationThe reaction was filtered through celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe crude 4-amino compound was dissolved in glacial acetic acid (3 mL)
  4. additionadded slowly to
  5. additionthen slowly added to
  6. extractionextracted with Et2O/EtOAc
  7. washThe combined organic extracts were washed with H2O and brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe product was purified by flash chromatography on a silica column
  11. washeluting with Hex/EtOAc/HOAc (80:20;1)

Sources & evidence

ORD record
ord-d25b025847f248c6bca0172b5493bee9
Source dataset
uspto-grants-1993_08
Patent number
US05240928

Reaction notes

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