Hydrochloric Acid → 6-(3-Chlorophenyl)-3-hexyl-6-methyl-3-azabicyclo[3.1.0]hexane

HRID 428861Notes

Reaction equation

HRID 428861 reaction equation
N([O-])=O.[Na+].[CH2:5]([N:11]1[CH2:16][CH:15]2[CH:13]([C:14]2([C:18]2[CH:19]=[C:20](N)[CH:21]=[CH:22][CH:23]=2)[CH3:17])[CH2:12]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C(=O)([O-])O.[Na+].[ClH:30]>O.[Cu]Cl>[Cl:30][C:20]1[CH:19]=[C:18]([C:14]2([CH3:17])[CH:15]3[CH:13]2[CH2:12][N:11]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:16]3)[CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 221413223-(3-Hexyl-6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenylamineHCID 23668193Sodium Nitrite

Product 1

HCID 221412126-(3-Chlorophenyl)-3-hexyl-6-methyl-3-azabicyclo[3.1.0]hexaneYield 39%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent

Procedure

A solution of sodium nitrite (97 mg, 1.4 mmol) dissolved in water (2 ml) was added to 3-(3-hexyl-6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenylamine (Preparation 12, 0.17 g, 0.61 mmol) dissolved in aqueous hydrochloric acid (2.0 M, 2 ml) over a few minutes at 0° C. After 30 min at 0° C., the reaction mixture was added to copper (I) chloride (1.57 g, 15.8 mmol) in concentrated hydrochloric acid (4.0 ml). After stirring the reaction mixture at room temperature for 45 min, the reaction mixture was heated to 90° C. for 5 min. The reaction mixture was poured cautiously on to solid, pre-wetted sodium hydrogen carbonate and the product was extracted firstly with diethyl ether and then ethyl acetate. The combined organic extracts were dried (MgSO4) and then concentrated in vacuo. The crude residue was purified by chromatography on silica gel eluting with hexane:ethyl acetate (8:1) to give the product (69 mg, 39%).

Workup

  1. temperaturethe reaction mixture was heated to 90° C. for 5 min
  2. extractionthe product was extracted firstly with diethyl ether
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified by chromatography on silica gel eluting with hexane:ethyl acetate (8:1)

Sources & evidence

ORD record
ord-4efbbe06f9be4e1385e9997b5bbb7541
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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