Reaction #1726720

Reaction equation

TFA

2-hydroxy-5-(1H-tetrazol-5-yl)benzamide

1-Boc-4-piperidone

morpholine

→

1′-(tert-butyloxycarbonyl)-6-(1H-tetrazol-5-yl)spiro[1,3-benzoxazine-2,4′-piperidine]-4(3H)-one

Yield 21.6%

Solvents

dichloromethane

MeOH

Conditions

Workup

1. 1
   Temperatureis refluxed for 72 hr
2. 2
   OtherThe MeOH is removed by rotoevapoation
3. 3
   Otherthe residue is purified by preparative TLC

Procedure

A mixture of 75 mg (0.37 mmol) of 2-hydroxy-5-(1H-tetrazol-5-yl)benzamide, 110 mg (0.55 mmol) of 1-Boc-4-piperidone, and 71 μL of morpholine in 8 mL of MeOH is refluxed for 72 hr. The MeOH is removed by rotoevapoation and the residue is purified by preparative TLC to give 29 mg (0.08 mmol, 15% yield) of 1′-(tert-butyloxycarbonyl)-6-(1H-tetrazol-5-yl)spiro[1,3-benzoxazine-2,4′-piperidine]-4(3H)-one which on treatment with 40% TFA in dichloromethane at room temperature for 3 hr. gives the TFA salt of 6-(1H-tetrazol-5-yl)spiro[1,3-benzoxazine-2,4′-piperidine]-4(3H)-one in quantitative yield.

Source