Triethylamine → 5-Methyl-1-(cyclohexylcarbohydroximoyl)-tetrazole

To a solution of cyclohexane carboxaldehyde oxime (35.6 g, 280 mmol) in DMF (300 ml) is added N-chlorosuccinimide (39.2 g, 294 mmol) portionwise, while maintaining the reaction temperature below 45° C. On complete addition, the mixture is stirred overnight at room temperature before adding a saturated aqueous NH4Cl solution (900 ml). The mixture is extracted with ethyl acetate. The organic layer is washed successively with water (500 ml) and brine (500 ml), dried (MgSO4), filtered and concentrated. The residue and 5-methyltetrazole (24.7 g, 294 mmol) are diluted in dichloromethane (400 ml) and triethyamine (50.8 ml, 364 mmol) is added dropwise at room temperature. After stirring overnight, the mixture in concentrated and the residue is taken up in ethyl acetate. The solution is washed successively with a saturated aqueous NH4Cl solution, water and brine, then dried (MgSO4), filtered and concentrated. Silica-gel chromatography of the residue affords 16.6 g of 5-methyl-1-(cyclohexylcarbohydroximoyl)-tetrazole [yield 28.3%; 1H-NMR (CDCl3) δppm: 1.1-1.5 (m, 4H), 1.62-1.98 (m, 6H), 2.55 (s, 3H), 2.8 (m, 1H), 9.3 (broad, 1H); HPLC/MS: m/z=210 (M+H)].

1. temperaturewhile maintaining the reaction temperature below 45° C
2. additionOn complete addition
3. extractionThe mixture is extracted with ethyl acetate
4. washThe organic layer is washed successively with water (500 ml) and brine (500 ml)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. stirringAfter stirring overnight
9. concentrationthe mixture in concentrated
10. washThe solution is washed successively with a saturated aqueous NH4Cl solution, water and brine
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-2e4489d7e1f44de48fe65f4349b085b2

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119646B2