Triethylamine → 2,3-Dihydro-2,4,6,7-tetramethyl-2-[[4-(4-pyridyl)-1-piperidinyl]methyl]-5-benzofuranamine

HRID 565626Notes

Reaction equation

Br[CH2:2][C:3]1([CH3:16])[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1.[NH:17]1[CH2:22][CH2:21][CH:20]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[CH2:19][CH2:18]1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(OCC)(=O)C>[CH3:16][C:3]1([CH2:2][N:26]2[CH2:27][CH2:28][CH:23]([C:20]3[CH:19]=[CH:18][N:17]=[CH:22][CH:21]=3)[CH2:24][CH2:25]2)[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1

Participants

Conditions

Temperature: 180 °C

Procedure

In an autoclave, a mixture of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine (0.85 g), 4-(4-piperidinyl)pyridine (0.97 g), and triethylamine (1.3 mL) was stirred under nitrogen gas at 180° C. for 15 hours. To this reaction mixture were added saturated aqueous NaHCO3 and ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=20.1) and crystallized from ethyl acetate/hexane to provide 0.77 g of the title compound. Yield 70%.

Workup

customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate
washThe pooled organic layer was washed with water and saturated aqueous NaCl
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (chloroform:methanol=20.1)
customcrystallized from ethyl acetate/hexane

Sources & evidence

ORD record: ord-cddf410d28a64f05aacf418c04287ccf
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06172085B2

Reaction notes

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