Réaction #3139

Équation de réaction

acetic anhydride

4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

acetic anhydride

diisopropylethylamine

→

title compound

4-(4-Acetamido-4-phenylpiperidino)-N-acetyl-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Solvants

hydrochloric acid

dichloromethane

water

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Températureto reflux for 3 hours
2. 2
   Températureto cool
3. 3
   AutreThe phases were separated
4. 4
   Extractionthe aqueous layer was extracted with dichloromethane (2×5 mL)
5. 5
   LavageThe combined organic phases were washed (brine)
6. 6
   Autredried
7. 7
   Autreevaporated
8. 8
   Autreto afford crude product, which
9. 9
   Autrewas purified by chromatography with dichloromethane:methanol (15:1) as eluent

Mode opératoire

To a stirred solution of 4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine (0.4 g) in tetrahydrofuran (4 mL) was added acetic anhydride (0.085 mL) and diisopropylethylamine (0.32 mL). After 2 hours at room temperature 4-dimethylaminopyridine (7 mg) was added and the mixture was stirred overnight. Additional acetic anhydride (0.06 mL) was added and the reaction mixture was brought to reflux for 3 hours. The mixture was allowed to cool and diluted with aqueous hydrochloric acid (1N, 3 mL), dichloromethane (5 mL), and water (5 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×5 mL). The combined organic phases were washed (brine), dried, and evaporated to afford crude product, which was purified by chromatography with dichloromethane:methanol (15:1) as eluent, to afford the title compound as a white solid; mp 115°-117° C.; NMR (d6 -DMSO-trifluoroacetic acid): 8.0-7.5 (m,5), 7.45-7.2 (m,6), 4.80-4.45 (m,2), 3.45 (m,2), 3.1 (m,4), 2.67 (m,1), 2.67 (m,2), 2.55 (s,3), 1.95 (s,3), 2.0 (broad m,5); MS: m/z=702(M+1,100%). Analysis for C34H35Cl2F6N3O2.1.50 H2O: Calculated: C, 55.97; H, 5.25; N, 5.76; Found: C, 55.91; H, 5.11; N, 5.76.

Source