Reaktion #1017453

Reaktionsgleichung

3,3-dimethylcyclohexanone

hydroxylamine hydrochloride

→

3,3-dimethylcyclohexanamine HCl

Lösungsmittel

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturheating
2. 2
   Sonstige(60° C.)
3. 3
   Sonstigefor 12 h
4. 4
   FiltrationAfter that time, the solution was filtered
5. 5
   Einengenconcentrated

Vorschrift

A 100 mL RBF was charged with 3,3-dimethylcyclohexanone (3.48 g, 27.6 mmol), hydroxylamine hydrochloride (2.01 g, 29.0 mmol), and 20 mL of MeOH. This mixture was heated to 60° C. for 1 h. To this solution was added Raney Nickel (approx 300 mg). This mixture was placed under a hydrogen atmosphere (1 atm) and heating was continued (60° C.) for 12 h. After that time, the solution was filtered, acidified with 1M HCl, and concentrated to give 3,3-dimethylcyclohexanamine HCl as an off-white solid. Step 2: A 20 mL vial was charged with (R)-3-(2-(tert-butylamino)-6-o-tolylquinolin-3-yl)-2-methylpropanoic acid (0.13 g, 0.33 mmol, prepared as in Example 8, Step 3-6), 3,3-dimethylcyclohexanaminium chloride (0.068 g, 0.42 mmol), TBTU (0.13 g, 0.42 mmol), and 2 mL of NMP. To this was added Hünig's base (0.11 g, 0.83 mmol). After stirring at RT for 2 h, the mixture was diluted with water and extracted with EtOAc. The combined organic layers were dried and concentrated to give an oil, which was purified via silica gel column chromatography to give the t-Bu protected amide intermediate. To this material, was added 3 mL of TFA and 3 mL of DCM. This mixture was heated at 40° C. for 12 h, then concentrated and purified by silica gel column chromatography (0-8% NH3/MeOH in CH2Cl2) to give (2R)-3-(2-amino-6-o-tolylquinolin-3-yl)-N-(3,3-dimethylcyclohexyl)-2-methylpropanamide as a white solid. MS (ESI, pos. ion) m/z: 430 (M+1).

Quelle