(1S,3S,4S)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine (1R,3R,4R)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine → (1S,3S,4S)-N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine (1R,3R,4R)-N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine

HRID 1963907Notes

Reaction equation

HRID 1963907 reaction equation
[N:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([N:10]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][C@@H:5]1[CH3:25])=[N+]=[N-].[N:26]([C@@H:29]1[CH2:34][CH2:33][C@@H:32]([N:35]([CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:31][C@H:30]1[CH3:50])=[N+]=[N-]>C(O)(=O)C.Cl.C(OCC)C.[Zn]>[CH2:18]([N:10]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C@H:7]1[CH2:8][CH2:9][C@H:4]([NH2:1])[C@@H:5]([CH3:25])[CH2:6]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1.[CH2:43]([N:35]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@@H:32]1[CH2:33][CH2:34][C@@H:29]([NH2:26])[C@H:30]([CH3:50])[CH2:31]1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

6

Reactant 1

HCID 86650616(1S,3S,4S)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine (1R,3R,4R)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine

Product 1

HCID 86650619(1S,3S,4S)-N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine (1R,3R,4R)-N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine

Reagents, catalysts & solvents 4

HCID 23994ZincCatalyst2×HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of (1S,3S ,4S)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine/(1R,3R,4R)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine (2.174 g, 6.5 mmol) in acetic acid (50 mL) was added slowly Zn-dust (0.638 g, 9.75 mmol). The mixture was stirred for 30 min at ambient temperature. Additional Zn-dust was added (150 mg) and stirring was continued for ˜15 min. The mixture was diluted carefully with 1N aqueous HCl and diethylether. The separated aqueous layer was extracted with diethylether (5ט100 mL). The aqeuous layer was partially lyophilized and concentrated to dryness in vacuo. The resulting residue was diluted with 1N aqueous HCl and concentration to dryness was repeated. Dilution with 1N HCl and concentration was repeated. The resulting residue was dissolved in water/acetonitrile and lyophilized to provide crude (1S,3S ,4S)—N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine/(1R,3R,4R)—N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine as fluffy white solid. The crude material was directly used in the next step without further purification. Yield: 2.292 g. LCMS (m/z): 309.3 [M+H]+; Retention time=0.50 min.

Workup

  1. stirringstirring
  2. waitwas continued for ˜15 min
  3. extractionThe separated aqueous layer was extracted with diethylether (5ט100 mL)
  4. concentrationconcentrated to dryness in vacuo
  5. additionThe resulting residue was diluted with 1N aqueous HCl and concentration to dryness
  6. concentrationDilution with 1N HCl and concentration
  7. dissolutionThe resulting residue was dissolved in water/acetonitrile

Sources & evidence

ORD record
ord-33d5a59baf314ffebdfa4e60c078215f
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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