4-(3-Bromophenoxy)butanoic acid → 8-Bromo-3,4-dihydrobenzo[b]oxepin-5(2H)-one

HRID 2385579Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[O:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=O>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:14]=[CH:13][C:12]2[C:9](=[O:11])[CH2:8][CH2:7][CH2:6][O:5][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a stirred suspension of polyphosphoric acid (PPA, ca. 60 g) and celite (ca. 40 g) in 100 mL toluene was added crude 4-(3-bromophenoxy)butanoic acid (ca. 58 mmol) in one portion, 10 mL toluene rinse. The resultant suspension was heated at 110° C. for 5 hr. The toluene was decanted through a plug of celite and the remaining slurry was washed repeatedly with toluene and ethylacetate. The eluent was concentrated and purified by flash column chromatography (4:1 hex:EtOAc) to give 8-bromo-3,4-dihydrobenzo[b]oxepin-5(2H)-one (7 g, ca. 50% yield). 1H NMR (DMSO-d6, 500 MHz) 7.55 (d, J=8.5 Hz, 1H), 7.37 (d, J=1.5 Hz, 1H), 7.35 (dd, J=8.5, 1.5 Hz, 1H), 4.24 (t, J=6.5 Hz, 2H), 2.79 (t, J=7.0 Hz, 2H), 2.14 (m, 2H).

Workup

washrinse
customThe toluene was decanted through a plug of celite
washthe remaining slurry was washed repeatedly with toluene and ethylacetate
concentrationThe eluent was concentrated
custompurified by flash column chromatography (4:1 hex:EtOAc)

Sources & evidence

ORD record: ord-acb38019444d49ea9232fc8b010ad55c
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08263633B2

Reaction notes

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