Dimethylformamide → (E)-7'-bromo-4'-fluoro-2'-(neopentyloxy)-6,7-dihydro-2H-spiro[[1,4]oxazepine-3,9'-xanthen]-5-amine

HRID 529401Notes

Reaction equation

[NH2:1][C:2]1=[N:3][C:4]2([CH2:21][O:22][CH2:23][CH2:24]1)[C:17]1[CH:16]=[C:15]([OH:18])[CH:14]=[C:13]([F:19])[C:12]=1[O:11][C:10]1[C:5]2=[CH:6][C:7]([Br:20])=[CH:8][CH:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.[CH2:36](I)[C:37]([CH3:40])([CH3:39])[CH3:38]>O>[Br:20][C:7]1[CH:6]=[C:5]2[C:10]([O:11][C:12]3[C:13]([F:19])=[CH:14][C:15]([O:18][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:16][C:17]=3[C:4]32[CH2:21][O:22][CH2:23][CH2:24][C:2]([NH2:1])=[N:3]3)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A vial was charged with (E)-5-amino-7′-bromo-4′-fluoro-6,7-dihydro-2H-spiro[[1,4]oxazepine-3,9′-xanthen]-2′-ol (222.7 mg, 0.566 mmol), cesium carbonate (738 mg, 2.265 mmol), and DMF (2832 μL) to give a yellow suspension. The resulting mixture was stirred for 10 min, then neopentyl iodide (225 μL, 1.699 mmol) was added. The vial was capped and heated to 100° C. for 2 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (0-10% MeOH/DCM) to give (E)-7′-bromo-4′-fluoro-2′-(neopentyloxy)-6,7-dihydro-2H-spiro[[1,4]oxazepine-3,9′-xanthen]-5-amine as a yellow oil.

Workup

customto give a yellow suspension
customThe vial was capped
extractionextracted with EtOAc (3×)
dry with materialThe combined organic extracts were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by chromatography on silica gel (0-10% MeOH/DCM)

Sources & evidence

ORD record: ord-be7e86ce9e28460f96178e4d7d16399e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346827B2

Reaction notes

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