1-Bromo-3-chloropropane → (1S,5R)-3-(3-chloropropyl)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

HRID 19670Notes

Reaction equation

HRID 19670 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C@:12]12[CH2:17][C@H:16]1[CH2:15][NH:14][CH2:13]2.Br[CH2:19][CH2:20][CH2:21][Cl:22]>O1CCCC1.C(N(CC)CC)C>[Cl:22][CH2:21][CH2:20][CH2:19][N:14]1[CH2:15][C@H:16]2[C@:12]([C:3]3[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=3[F:1])([CH2:17]2)[CH2:13]1

Participants

5

Reactant 2

HCID 80061-Bromo-3-chloropropaneHCID 59346768(1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 59346766(1S,5R)-3-(3-chloropropyl)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of (1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (P13, 426 mg) in dry tetrahydrofuran (9 mL), triethylamine (0.79 mL) and 1-bromo-3-chloropropane (0.37 mL) were added and the resulting mixture was refluxed for 16 hours. After cooling at room temperature it was concentrated in vacuo, diluted with ethyl acetate, washed with a saturated solution of NaHCO3 in water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by chromatography (silica gel) eluting with cyclohexane/EtOAc 8:2 to give the title compound as yellow oil (582 mg).

Workup

  1. temperaturethe resulting mixture was refluxed for 16 hours
  2. concentrationwas concentrated in vacuo
  3. additiondiluted with ethyl acetate
  4. washwashed with a saturated solution of NaHCO3 in water and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by chromatography (silica gel)
  8. washeluting with cyclohexane/EtOAc 8:2

Sources & evidence

ORD record
ord-cc47e96a7be6454cb713ea720f91b470
Source dataset
uspto-grants-2010_06
Patent number
US07745458B2

Reaction notes

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