1-Bromo-4-fluorobenzene → HCID 68056120, compound

HRID 340628Notes

Reaction equation

HRID 340628 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](F)=[CH:4][CH:3]=1.[CH:9]1([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:11][CH2:10]1.CCN(C(C)C)C(C)C>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:15]2[CH2:16][CH2:17][CH:12]([CH:9]3[CH2:11][CH2:10]3)[CH2:13][CH2:14]2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 81531DiisopropylethylamineHCID 450927774-Cyclopropylpiperidine

Product 1

HCID 68056120HCID 68056120, compound

Procedure

A round bottomed flask was charged with 1-bromo-4-fluorobenzene (1.93 g, 11.0 mmol), 4-cyclopropylpiperidine (1.65 g, 13.2 mmol) and DIEA (7.67 g, 44.0 mmol). The flask was purged with nitrogen. Anhydrous 1-methyl-2-pyrrolidinone (25 mL) was added, and the resulting mixture was degassed via nitrogen sparge. The mixture was then placed in a pre-heated oil bath (180° C.), and was held at this temperature for 2 days, whereupon it was allowed to cool to ambient temperature, then was poured into water. The aqueous phase was extracted with ethyl acetate and the organic phase was washed with brine. The organic phase was then dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by chromatography on silica gel (0 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 281.8 [M+H]+; 1H NMR (500 MHz, CD2Cl2) δ 7.30 (d, J=8.8 Hz, 2 H),6.79 (d, J=8.8 Hz, 2 H),3.62 (d, J=12.2 Hz, 2 H),2.62 (t, J=12.1 Hz, 2 H),1.83 (d, J=12.8 Hz, 2 H),1.56-1.42 (m, 2 H),0.69-0.53 (m, 2 H),0.41 (d, J=7.5 Hz, 2 H),0.11 (d, J=4.5 Hz, 2 H).

Workup

  1. customThe flask was purged with nitrogen
  2. additionAnhydrous 1-methyl-2-pyrrolidinone (25 mL) was added
  3. customthe resulting mixture was degassed via nitrogen
  4. customsparge
  5. customThe mixture was then placed in a pre-heated oil bath
  6. additionwas poured into water
  7. extractionThe aqueous phase was extracted with ethyl acetate
  8. washthe organic phase was washed with brine
  9. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customPurification by chromatography on silica gel (0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-96649b6a24964603adf6ddb65f9f5faf
Source dataset
uspto-grants-2014_11
Patent number
US08895583B2

Reaction notes

Loading…