Iodoethane → 1-(3,4-Dichlorophenyl)-3-(propan-2-yl)-3-azabicyclo[3.1.0]hexane

HRID 1256645Notes

Reaction equation

HRID 1256645 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:10]23[CH2:15][CH:14]2[CH2:13][NH:12][CH2:11]3)[CH:6]=[CH:7][C:8]=1[Cl:9].ICC.CCN(C(C)C)[CH:22]([CH3:24])[CH3:23]>CN(C=O)C>[Cl:2][C:3]1[CH:4]=[C:5]([C:10]23[CH2:15][CH:14]2[CH2:13][N:12]([CH:22]([CH3:24])[CH3:23])[CH2:11]3)[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 81531DiisopropylethylamineHCID 97952751-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane Hydrochloride

Product 1

HCID 160468141-(3,4-Dichlorophenyl)-3-(propan-2-yl)-3-azabicyclo[3.1.0]hexaneYield 146.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-(3,4-dichlorophenyl)-3-aza-bicyclo[3.1.0]hexane hydrochloride (10.0 g, 43.8 mmol) in DMF (20 mL) was added 2-iodoethane (9.67 g, 56.9 mmol) and DIPEA (7.35 g, 56.9 mmol). The resulting solution was stirred at ambient temperature for 6 h. After this time, the solvent was removed under vacuum and the residue was dissolved in CH2Cl2 (50 mL). The organic layer was washed with water (2×50 mL), 2N sodium hydroxide (50 mL) and brine (50 mL). The organics were dried (Na2SO4) and concentrated under vacuum. Three reactions were run in parallel and then combined for purification via column chromatography (silica gel, EtOAc) to provide the title compound (17.3 g, 49% yield) as a yellow oil: LC (ELS)/MS: 91%, m/z 271.6 [C14H17Cl2N+H]+; 1H NMR (300 MHz, CDCl3): δ 0.75 (dd, 1H, J=4.2 Hz, J=8.1 Hz), 1.05 (dd, 6H, J=4.7 Hz, J=6.3 Hz), 1.44 (t, 1H, J=4.2 Hz), 1.67 (td, 1H, J=3.9 Hz, J=8.0 Hz), 2.50 (m, 3H), 3.11 (d, 1H, J=8.6 Hz), 3.31 (d, 1H, J=8.4 Hz), 6.96 (dd, 1H, J=2.1 Hz, J=8.3 Hz), 7.22 (d, 1H, J=2.1 Hz), 7.32 (d, 1H, J=8.3 Hz).

Workup

  1. customAfter this time, the solvent was removed under vacuum
  2. dissolutionthe residue was dissolved in CH2Cl2 (50 mL)
  3. washThe organic layer was washed with water (2×50 mL), 2N sodium hydroxide (50 mL) and brine (50 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customthen combined for purification via column chromatography (silica gel, EtOAc)

Sources & evidence

ORD record
ord-9724ca23b1f248df81a8f58427ba3d79
Source dataset
uspto-grants-2013_06
Patent number
US08461196B2

Reaction notes

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