1-Bromo-4-fluorobenzene → HCID 62602864, compound

HRID 1803213Notes

Reaction equation

HRID 1803213 reaction equation
[C:1]1(=[O:8])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1.CC(C)([O-])C.[Na+]>C1COCC1.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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[F:16][C:13]1[CH:14]=[CH:15][C:10]([CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:1]2=[O:8])=[CH:11][CH:12]=1

Participants

7

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 10400CycloheptanoneHCID 23676156Sodium t-butoxide

Product 1

HCID 62602864HCID 62602864, compoundYield 38.9%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Step AAF (1): A mixture of cycloheptanone (1.0 g, 8.92 mmol), 1-bromo-4-fluorobenzene (0.874 g, 4.99 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.067 g, 0.116 mmol), sodium tert-butoxide (1.157 g, 11.68 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.049 g, 0.053 mmol) in THF (10 mL) was heated at 80° C. overnight. The crude product was purified by Prep-HPLC (Solvent A=10% MeOH-90% water-0.1% TFA, Solvent B=90% MeOH-10% water-0.1% TFA. Column: Phenomenex Luna 30×100 mm, S10, Flow rate: 40 ml/min, 45-100% B, 30 min) to obtain 2-(4-fluorophenyl)cycloheptanone (400 mg, 1.94 mmol, 22% yield). LC-MS (M+H)+=207.2. 1H NMR (400 MHz, methanol-d4) δ ppm 7.13-7.31 (m, 2 H) 6.91-7.08 (m, 2 H) 3.68-3.86 (m, 1 H) 2.58-2.76 (m, 1 H) 2.42-2.57 (m, 1 H) 1.85-2.13 (m, 5 H) 1.57-1.75 (m, 1 H) 1.35-1.57 (m, 2 H).

Workup

  1. customThe crude product was purified by Prep-HPLC (Solvent A=10% MeOH-90% water-0.1% TFA, Solvent B=90% MeOH-10% water-0.1% TFA. Column: Phenomenex Luna 30×100 mm, S10, Flow rate: 40 ml/min, 45-100% B, 30 min)

Sources & evidence

ORD record
ord-5756204a9c5d4d458da1d265205a494b
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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