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

HRID 2265076Notes

Reaction equation

HRID 2265076 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][NH:11][CH2:10]3)=[CH:5][CH:4]=1.Br[CH2:18][CH2:19][CH2:20][Cl:21]>O1CCCC1.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>[Cl:21][CH2:20][CH2:19][CH2:18][N:11]1[CH2:12][C@H:13]2[C@:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=3)([CH2:14]2)[CH2:10]1

Participants

6

Reactant 2

HCID 80061-Bromo-3-chloropropaneHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 59337588(1S,5R)-3-(3-chloropropyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (1.00 g) in dry tetrahydrofuran (5 mL), diisopropylethylamine (2.4 mL) and 1-bromo-3-chloropropane (3.7 mL) were added and the resulting mixture was heated at reflux for 3 hours. After cooling at room temperature it was diluted with ethyl acetate (30 mL) washed twice with a saturated solution of NH4Cl in water (20 mL) and once with a saturated solution of NaHCO3 in water (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with cyclohexane/EtOAc 7:3 to give the title compound as a colourless oil (1.26 g).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 3 hours
  3. washwashed twice with a saturated solution of NH4Cl in water (20 mL) and once with a saturated solution of NaHCO3 in water (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by silica gel chromatography
  7. washeluting with cyclohexane/EtOAc 7:3

Sources & evidence

ORD record
ord-2c45aa722de046529edc38b29537c557
Source dataset
uspto-grants-2010_12
Patent number
US07855298B2

Reaction notes

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