Reaktion #70073

Reaktionsgleichung

5-[4′-(bromomethyl)biphenyl-2-yl]-1-(p-methoxybenzyl)-1H-tetrazole

compound 5a

5-[4′-(bromomethyl)biphenyl-2-yl]-1-(p-methoxybenzyl)-1H-tetrazole

acetonitrile

methyl 2-(tert-butoxycarbonylamino)-3-nitrobenzoate

compound 19a

methyl 2-(tert-butoxycarbonylamino)-3-nitrobenzoate

potassium carbonate

→

methyl 2-(N-tert-butoxycarbonyl-N-{(2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl)methyl}amino)-3-nitrobenzoate

Lösungsmittel

toluene ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturunder reflux for 6 hr under a nitrogen atmosphere
3. 3
   TemperaturThe reaction mixture was cooled
4. 4
   Filtrationfiltered
5. 5
   Waschenthe cake was washed with acetonitrile (35 mL)
6. 6
   EinengenThe filtrate was concentrated under reduced pressure at 35° C.
7. 7
   Sonstigelower to give a crude product
8. 8
   SonstigeThe crude product was purified by silica gel column chromatography (eluent: toluene/ethyl acetate (100:0-4:1))
9. 9
   Einengenthe fraction was concentrated
10. 10
    workup.ADDITIONTo the residue was added chloroform (about 30 ml)
11. 11
    Einengenthe mixture was concentrated
12. 12
    SonstigeThe residue was dried under reduced pressure in a bath at 40° C.

Vorschrift

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%)).

Quelle