Dichloromethane → biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenyl-carbamoyl)ethyl]piperidin-4-yl ester

To a 1 L round-bottom flask was added biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(3-formylamino-4-hydroxyphenyl)ethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (21.5 g, 27.1 mmol) and dichloromethane (200 mL). The resulting mixture was stirred at room temperature until the ingredients dissolved and then triethylamine trihydrofluoride (8.85 mL, 54.2 mmol) was added and the resulting mixture was stirred at 25° C. for about 48 hours. The solvent was removed on a rotary evaporator to provide a thick paste. Dichloromethane (100 mL) and ethyl acetate (200 mL) were added to the paste and the resulting mixture was stirred for 30 minutes. The resulting slurry was slowly filtered under dry nitrogen and the filter cake was washed with a 1:2 mixture of dichloromethane and ethyl acetate (100 mL total), dried under nitrogen for 2 hours and then dried under vacuum overnight to provide biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester as a hydrofluoride salt (25 g, 96.9% purity) which was a hard clay-like solid. MS [M+H+] found 680.8.

1. dissolutiondissolved
2. stirringthe resulting mixture was stirred at 25° C. for about 48 hours
3. customThe solvent was removed on a rotary evaporator
4. customto provide a thick paste
5. stirringthe resulting mixture was stirred for 30 minutes
6. filtrationThe resulting slurry was slowly filtered under dry nitrogen
7. washthe filter cake was washed with a 1:2 mixture of dichloromethane and ethyl acetate (100 mL total)
8. customdried under nitrogen for 2 hours
9. customdried under vacuum overnight

ORD-Eintrag

ord-13566b0fc4ba4996a0736b021a194f0d

Quelldatensatz

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07524965B2