تفاعل #70073

ord-701a9bd0582d4b59bcee3196b82aab71

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةwas heated
  2. 2
    درجة الحرارةunder reflux for 6 hr under a nitrogen atmosphere
  3. 3
    درجة الحرارةThe reaction mixture was cooled
  4. 4
    ترشيحfiltered
  5. 5
    غسيلthe cake was washed with acetonitrile (35 mL)
  6. 6
    تركيزThe filtrate was concentrated under reduced pressure at 35° C.
  7. 7
    أخرىlower to give a crude product
  8. 8
    أخرىThe crude product was purified by silica gel column chromatography (eluent: toluene/ethyl acetate (100:0-4:1))
  9. 9
    تركيزthe fraction was concentrated
  10. 10
    workup.ADDITIONTo the residue was added chloroform (about 30 ml)
  11. 11
    تركيزthe mixture was concentrated
  12. 12
    أخرىThe residue was dried under reduced pressure in a bath at 40° C.

الإجراء التجريبي

A mixture of 5-[4′-(bromomethyl)biphenyl-2-yl]-1-(p-methoxybenzyl)-1H-tetrazole (compound 5a, 9.25 g, 21.2 mmol), acetonitrile (107 ml), methyl 2-(tert-butoxycarbonylamino)-3-nitrobenzoate (compound 19a, 6.43 g, 21.7 mmol) and potassium carbonate (3.00 g, 21.7 mmol) was heated under reflux for 6 hr under a nitrogen atmosphere. The reaction was monitored by TLC (eluent: toluene/ethyl acetate (4:1)). The reaction mixture was cooled, and filtered, and the cake was washed with acetonitrile (35 mL). The filtrate was concentrated under reduced pressure at 35° C. or lower to give a crude product. The crude product was purified by silica gel column chromatography (eluent: toluene/ethyl acetate (100:0-4:1)), and the fraction was concentrated. To the residue was added chloroform (about 30 ml), and the mixture was concentrated. The operations were repeated four times. The residue was dried under reduced pressure in a bath at 40° C. to give methyl 2-(N-tert-butoxycarbonyl-N-{(2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl)methyl}amino)-3-nitrobenzoate (compound 20a) as a yellowish brown amorphous solid (9.83 g (71.1%)).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08530506B2uspto-grants-2013_09