Reaktion #1777177

Reaktionsgleichung

Isobutylamine

1-[2-(2-Methoxyphenyl)-7-methylquinazolin-4-yl]-piperidin-4-ol

phosgene

→

carbamate

Ausbeute 66.7%

Isobutylcarbamic acid 1-[2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl]-piperidin-4-yl ester

Ausbeute 66.7%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGby stirring at room temperature for 1 hour
2. 2
   SonstigeThe mixture was evaporated to dryness
3. 3
   Sonstigethe obtained residue was purified via silica gel chromatography

Vorschrift

To a stirring solution of 1-[2-(2-Methoxyphenyl)-7-methylquinazolin-4-yl]-piperidin-4-ol (100 mg, 0.30 mmol) and THF (500 μL) under N2, was added phosgene (317 μL, 0.60 mmol, 20% in toluene). The mixture was stirred at room temperature for 15 minutes. Isobutylamine (300 μL, 3.0 mmol) was added dropwise over a 2 minute period followed by stirring at room temperature for 1 hour. The mixture was evaporated to dryness and the obtained residue was purified via silica gel chromatography using 97% CH2Cl2/3% MeOH to obtain the desired carbamate intermediate as a clear oil (90 mg, 0.20 mmol). To a stirring solution of the carbamate intermediate (90 mg, 0.20 mmol) and CH2Cl2 (15 mL), under N2, at −78° C., was added BBr3 (0.60 mL, 0.60 mmol, 1.0 M in CH2Cl2) dropwise over a period of 2 minutes. The mixture was then allowed to warm to room temperature and was then heated at 50° C. for 15 minutes. The mixture was poured into a saturated aqueous NaHCO3 solution (80 mL) and the organic portion was evaporated to dryness. The residue was purified via HPLC to obtain the desired carbamate as a TFA salt (66 mg, 0.12 mmol, 39% yield). LC/MS (10-99%) M/Z 435.3 retention time 3.08 min.

Quelle