Hydrochloric Acid → benzyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

A mixture of benzyl((S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methylcarbamate (0.20 g, 0.60 mmol) and 4 M HCl in dioxane (10 mL) was stirred for 3 h at room temperature. After evaporating the solvent under reduced pressure, the solid was triturated with Et2O, dried under vacuum, and taken up in CH2Cl2 (10 mL). 2-(4-Chloro-7-methylquinazolin-2-yl)phenol (0.16 g, 0.60 mmol) was added to this solution, followed by the addition of triethylamine (0.25 mL, 1.8 mmol). The reaction mixture was stirred at room temperature overnight, then diluted with CH2Cl2 and washed with water. The combined organic layers were dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-40% EtOAc in hexanes gave benzyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate as a colorless oil (0.19 g, 68% yield). LC/MS: m/z 469.1 (M+H)+ at 2.58 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

1. customAfter evaporating the solvent under reduced pressure
2. customthe solid was triturated with Et2O
3. customdried under vacuum
4. stirringThe reaction mixture was stirred at room temperature overnight
5. washwashed with water
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification via silica gel chromatography

ORD-Eintrag

ord-3d96a54a322e4211adddee8be47fab04

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08283354B2