1,2-Difluorobenzene → HCID 67437137, compound

HRID 1879371Notes

Reaction equation

HRID 1879371 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].[Li]CCCC.[CH:14]([Si:17]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[O:18][C@@H:19]1[C:25]2=[N:26][CH:27]=[CH:28][CH:29]=[C:24]2[CH2:23][C:22](=[O:30])[CH2:21][CH2:20]1)([CH3:16])[CH3:15]>O1CCCC1>[F:1][C:2]1[C:3]([F:8])=[CH:4][CH:5]=[CH:6][C:7]=1[C@:22]1([OH:30])[CH2:21][CH2:20][C@H:19]([O:18][Si:17]([CH:31]([CH3:33])[CH3:32])([CH:34]([CH3:36])[CH3:35])[CH:14]([CH3:15])[CH3:16])[C:25]2=[N:26][CH:27]=[CH:28][CH:29]=[C:24]2[CH2:23]1

Participants

5

Reactant 3

HCID 97061,2-DifluorobenzeneHCID 67438705HCID 67438705, compoundHCID 178418339Butyllithium

Product 1

HCID 67437137HCID 67437137, compoundYield 79.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-65 °C

Procedure

In an oven-dried 250 mL round-bottom flask was dissolved 1,2-difluorobenzene (0.680 mL, 6.90 mmol) in tetrahydrofuran (12 mL) under nitrogen. After cooling to −65° C., n-BuLi (1M in hexanes, 2.208 mL, 5.52 mmol) was added dropwise via syringe. After the mixture was stirred between −65 and −60° C. for 30 min, it was cooled down to −78° C. A solution of (S)-9-(triisopropylsilyloxy)-8,9-dihydro-5H-cyclohepta[b]pyridin-6(7H)-one (920.5 mg, 2.76 mmol) (80304-043) in tetrahydrofuran (4 mL plus 4 mL rinse) was added via syringe (turned to yellow) and the reaction was stirred at −78° C. for 1 h (yellow color), and at room temperature for 30 min (red color). LCMS indicated good conversion. The reaction was quenched by saturated NH4Cl solution. Tetrahydrofuran was removed and the residue was partitioned between water and ethyl acetate. The layers were separated. The organic layer was washed with brine, dried with sodium sulfate, and concentrated to give a tan oil. Purification by FCC up to 80% ethyl acetate/hexane afforded the recovered SM (197 mg, 21%) as a yellow oil as well as the desired products (977 mg, 79%) as a colorless oil. MS(ESI)[M+H+]=448.33; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.26 (d, J=3.53 Hz, 1H) 7.42 (t, J=6.42 Hz, 1H) 7.35 (d, J=7.30 Hz, 1H) 6.99-7.13 (m, 3H) 5.16 (br. s., 1H) 4.63 (d, J=13.85 Hz, 1H) 3.02-3.28 (m, 1H) 2.71 (d, J=14.10 Hz, 1H) 2.34 (d, J=4.03 Hz, 1H) 2.02-2.15 (m, 2H) 1.75 (d, J=13.85 Hz, 1H) 1.06-1.19 (m, J=14.67, 7.27, 7.27, 7.05 Hz, 3H) 0.97-1.07 (m, 9H) 0.84-0.97 (m, 9H).

Workup

  1. temperatureit was cooled down to −78° C
  2. stirringthe reaction was stirred at −78° C. for 1 h (yellow color)
  3. waitat room temperature for 30 min (red color)
  4. customThe reaction was quenched by saturated NH4Cl solution
  5. customTetrahydrofuran was removed
  6. customthe residue was partitioned between water and ethyl acetate
  7. customThe layers were separated
  8. washThe organic layer was washed with brine
  9. dry with materialdried with sodium sulfate
  10. concentrationconcentrated
  11. customto give a tan oil
  12. customPurification by FCC up to 80% ethyl acetate/hexane

Sources & evidence

ORD record
ord-551ae852b07b409e885dbdaa589489ba
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

Loading…