1-Bromo-2,3-difluorobenzene → HCID 57911456, compound

HRID 1099161Notes

Reaction equation

HRID 1099161 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[F:9].[N:10]1[CH:15]=[CH:14][CH:13]=[C:12]2[CH2:16][C:17](=[O:21])[CH2:18][CH2:19][CH2:20][C:11]=12>C1COCC1>[F:9][C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[C:17]1([OH:21])[CH2:18][CH2:19][CH2:20][C:11]2=[N:10][CH:15]=[CH:14][CH:13]=[C:12]2[CH2:16]1

Participants

4

Reactant 2

HCID 27332601-Bromo-2,3-difluorobenzeneHCID 57911419HCID 57911419, compound

Product 1

HCID 57911456HCID 57911456, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

In an oven-dried 500 mL round-bottomed flask was BuLi (17.19 mL, 43.0 mmol) in THF (100 mL) to give a colorless solution at −78° C. under nitrogen. 1-Bromo-2,3-difluorobenzene (4.81 mL, 43.0 mmol) was added dropwise via syringe. The mixture was stirred at −78° C. for 20 min, and 8,9-dihydro-5H-cyclohepta[b]pyridin-6(7H)-one (4.947 g, 30.7 mmol) (azeotroped with dry benzene and dried under high vac) dissolved in 10 ml THF was added dropwise via canuula (plus 10 ml THF rinse). The mixture was warmed up to rt in 1 h. TLC showed some conversion to a slightly more polar spot. After quenched with saturated NH4Cl solution, THF was stripped off. The remaining mixture was partitioned between water and EtOAc. The layers were separated and the organic layer was washed with brine, dried with Na2SO4, and concentrated to a dark oil. The residue was purified by FCC up to 10% MeOH/CH2Cl2 (very difficult separation). The impure fractions were pooled and purified by FCC with EtOAc/CH2Cl2 up to pure EtOAc. The recovered SM: 1.88 g (38%). The product fractions were pooled and concentrated to a tan solid, which were washed repeatedly with Et2O to a tan solid (1.79 g, 21%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.27 (dd, J=4.91, 1.38 Hz, 1H) 7.38-7.47 (m, 1H) 7.30-7.35 (m, 1H) 6.97-7.12 (m, 3H) 3.93 (dd, J=14.60, 2.52 Hz, 1H) 3.06-3.20 (m, 2H) 2.86 (dd, J=14.60, 1.76 Hz, 1H) 2.37-2.68 (m, 2H) 1.68-1.94 (m, 2H) 1.17 (t, J=7.05 Hz, 1H).

Workup

  1. temperatureThe mixture was warmed up to rt in 1 h
  2. customAfter quenched with saturated NH4Cl solution, THF
  3. customThe remaining mixture was partitioned between water and EtOAc
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated to a dark oil
  8. customThe residue was purified by FCC up to 10% MeOH/CH2Cl2 (
  9. customvery difficult separation)
  10. custompurified by FCC with EtOAc/CH2Cl2 up to pure EtOAc
  11. concentrationconcentrated to a tan solid, which
  12. washwere washed repeatedly with Et2O to a tan solid (1.79 g, 21%)

Sources & evidence

ORD record
ord-5d16cefd2bab4db19002ebe85418b9e0
Source dataset
uspto-grants-2012_03
Patent number
US08143403B2

Reaction notes

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