Sodium hydroxide--water (1/1/1) → 3-bromo-2-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one

HRID 1911031Notes

Reaction equation

HRID 1911031 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:4][C:3]=1[F:15].[OH-].[Na+].O>>[Br:1][C:2]1[C:3]([F:15])=[CH:4][C:5]2[CH2:8][CH2:9][CH2:10][CH2:11][C:12](=[O:14])[C:6]=2[CH:7]=1

Participants

3

Reactant 2

HCID 23719242Sodium hydroxide--water (1/1/1)HCID 710610425-(4-Bromo-3-fluorophenyl)pentanoic acid

Product 1

HCID 710609053-bromo-2-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-oneYield 57%

Conditions

Temperature
147.5 °C

Procedure

A mixture of 5-(4-bromo-3-fluorophenyl)pentanoic acid from step L2 (5.1 g, 18.54 mmol) in polyphosphoric acid (75 g, 18.5 mmol) was stirred at 145-150° C. for 3 h. After cooling to rt, the mixture was poured into ice, neutralized with 50% NaOH/water, and extracted with EtOAc/diethyl ether. The organic layer was dried over sodium sulfate and concentrated. The residue was purified via silica gel column chromatography (hexanes-8% EtOAc) to give 3-bromo-2-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one (2.7 g, 10.5 mmol, 57% yield). LCMS (M+H)+=257.0. 1H NMR (500 HMz, chloroform-d) δ 7.98 (d, J=7.3 Hz, 1H), 6.99 (d, J=8.9 Hz, 1H), 2.93-2.89 (m, 2H), 2.77-2.73 (m, 2H), 1.95-1.88 (m, 2H), 1.87-1.81 (m, 2H).

Workup

  1. temperatureAfter cooling to rt
  2. additionthe mixture was poured into ice
  3. extractionextracted with EtOAc/diethyl ether
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified via silica gel column chromatography (hexanes-8% EtOAc)

Sources & evidence

ORD record
ord-8aa4568240f24698af822dd61de3c25a
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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