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

HRID 1157729Notes

Reaction equation

HRID 1157729 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 (P4, 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 the mixture 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-a449460df66f49d087c737d2b5e1a383
Source dataset
uspto-grants-2010_10
Patent number
US07807698B2

Reaction notes

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