Cesium carbonate → (1R,5S)-3-(3-nitrophenyl)-8-oxa-3-azabicyclo[3.2.1]octane

HRID 1410065Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[CH:3]=1.Cl.[C@@H:12]12[O:19][C@@H:16]([CH2:17][CH2:18]1)[CH2:15][NH:14][CH2:13]2.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[N+:8]([C:4]1[CH:3]=[C:2]([N:14]2[CH2:13][C@H:12]3[O:19][C@H:16]([CH2:17][CH2:18]3)[CH2:15]2)[CH:7]=[CH:6][CH:5]=1)([O-:10])=[O:9]

Participants

Conditions

Temperature: 100 °C

Procedure

The mixture of 1-bromo-3-nitrobenzene (0.15 g, 0.743 mmol), (1R,5S)-8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (0.122 g, 0.82 mmol), Pd2(dba)3 (0.043 g, 0.074 mmol), X-Phos (0.071 g, 0.15 mmol) and Cs2CO3 (0.727 g, 2.23 mmol) in dioxane (30 mL) was heated to 100° C. for 16 h under N2 atmosphere. Then it was concentrated to dryness. The residue was purified by column chromatography (silica gel, 200˜300 mesh, eluting with ethyl acetate:petroleum ether=1:8) to afford (1R,5S)-3-(3-nitrophenyl)-8-oxa-3-azabicyclo[3.2.1]octane (0.12 g, 69%) as a brown solid. LC-MS: 235 [M+H]+, tR=1.57 min.

Workup

concentrationThen it was concentrated to dryness
customThe residue was purified by column chromatography (silica gel, 200˜300 mesh, eluting with ethyl acetate:petroleum ether=1:8)

Sources & evidence

ORD record: ord-3f5645e8a2c845679675f410eb609ca0
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921383B2

Reaction notes

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