Morpholine → N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetamide

HRID 1487202Notes

Reaction equation

Br[C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([NH:12][C:13](=[O:15])[CH3:14])=[CH:4][CH:3]=1.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:19]1[CH2:20][CH2:21][N:16]([C:2]2[C:7]3[O:8][CH2:9][CH2:10][O:11][C:6]=3[C:5]([NH:12][C:13](=[O:15])[CH3:14])=[CH:4][CH:3]=2)[CH2:17][CH2:18]1

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution of N-(8-bromo-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetamide (5 g, 18.4 mmol) in toluene (50 mL) was added morpholine (1.9 g, 22 mmol), Pd2(dba)3 (1.68 g, 1.84 mmol), X-Phos (1.75 g, 3.68 mmol) and potassium tert-butoxide (4.1 g, 36.8 mmol) in a sealed tube. The mixture was heated at 130° C. for overnight. After cooled to room temperature, the mixture was filtered and the filtrate was evaporated to give a crude product, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate 4/1) to afford the product N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetamide (2 g, yield 40%).

Workup

temperatureAfter cooled to room temperature
filtrationthe mixture was filtered
customthe filtrate was evaporated
customto give a crude product, which
customwas purified by silica gel column chromatography (petroleum ether/ethyl acetate 4/1)

Sources & evidence

ORD record: ord-07d64160d1cf4325b320ab0ffa0cae39
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428508B2

Reaction notes

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