Réaction #345473

Équation de réaction

water

isopropanol

sodium hydride

N,N-dimethylformamide

2-chloro-9-[4-(bromoacetamido)piperidinomethyl]methanoanthracene

→

title compound

Rendement 48.0%

N-(1-[2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]-4-piperidyl)-2-(isopropoxy)acetamide

Rendement 48.0%

Solvants

methylene chloride

Conditions de réaction

Traitement

1. 1
   TempératureTo a cooled (ice bath)
2. 2
   workup.STIRRINGAfter stirring for 0.5 h at 0° C.
3. 3
   workup.STIRRINGstirred for an additional 18 h
4. 4
   Filtrationfiltered through celite with methylene chloride (3×50 mL) washes
5. 5
   AutreAfter separating the aqueous layer from the filtrate
6. 6
   Lavagethe organic layer was washed with brine (50 mL)
7. 7
   Séchagedried (sodium sulfate)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated
10. 10
    Autreto give a yellow syrup

Mode opératoire

To a cooled (ice bath) stirred suspension of 97% sodium hydride (180 mg, 7.5 mmol) in N,N-dimethylformamide (3 mL) was added isopropanol (0.58 mL, 7.5 mmol). After stirring for 0.5 h at 0° C., the reaction was added 2-chloro-9-[4-(bromoacetamido)piperidinomethyl]methanoanthracene (575 mg, 1.25 mmol) and silver tetrafluoroborate (243 mg, 1.25 mmol). The reaction was allowed to warm to ambient temperature and stirred for an additional 18 h. The mixture was treated with water (50 mL) and methylene chloride (100 mL) and filtered through celite with methylene chloride (3×50 mL) washes. After separating the aqueous layer from the filtrate, the organic layer was washed with brine (50 mL), dried (sodium sulfate), filtered, and concentrated to give a yellow syrup. Chromatography of this material over silica gel (eluant: 9:1 methylene chloride/ether) gave the title compound as a light yellow glass (265 mg, 48%), mp 50.0°-3.0° C.; MS(CI): 439 (M+H); NMR (300 MHz,DMSO-d6): 1.10(d, 6H, J=6.0 Hz), 1.51-1.61(br m, 4H), 2.26(br m, 2H), 2.47(m, 2H), 2.93(br m, 2H), 3.29(d, part.submerged by H2O, 1H), 3.38(d, 1H, J=14.1 Hz), 3.57(septet, 1H, J=6.2 Hz), 3.62(br m, 1H), 3.78(s, 1H), 4.34(s, 1H), 6.96(br m, 3H), 7.20(br d, 2H, J=8.9 Hz), 7.27(d, 2H, J=7.7 Hz), 7.34(d, 1H, J=8.0 Hz).

Source