1,4-Dioxane hydrochloride → N-(Hexahydro-1H-azepin-4-ylmethyl)-trans-2-phenylcyclopropanamine

HRID 534157Notes

Reaction equation

HRID 534157 reaction equation
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][CH:12]2[CH2:18][CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O1CCOCC1>C(Cl)(Cl)Cl>[NH:15]1[CH2:16][CH2:17][CH2:18][CH:12]([CH2:11][NH:10][C@@H:8]2[CH2:9][C@H:7]2[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:13][CH2:14]1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 665716391,1-Dimethylethyl 4-({[trans-2-phenylcyclopropyl]amino}methyl)hexahydro-1H-azepine-1-carboxylate

Product 1

HCID 66571527N-(Hexahydro-1H-azepin-4-ylmethyl)-trans-2-phenylcyclopropanamineYield 80.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Chloroform (50 mL) was added to a 200 mL round-bottomed flask containing tert-butyl 4-(((trans-2-phenylcyclopropyl)amino)methyl)azepane-1-carboxylate (49.4 mg, 0.143 mmol) to give a suspension. HCl/1,4-Dioxane (12 mL, 48.0 mmol) was added and the mixture stirred 18 hour at room temperature. Upon completion, the residue was adsorbed directly onto silica and purified via column chromatography on the ISCO Companion (gradient 0-100% 80:20:2 [CHCl3/MeOH/NH4OH]/CHCl3; 4 g column). Fractions were collected, solvents removed and the resulting residue was taken up in MeOH (2 mL). Excess 2M HCl in Et2O and stirred for 10 minutes. The solvent was removed to yield the 2HCl salt of the desired product (28 mg, 59% yield) as a yellow solid: LC-MS (ES) m/z=245 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.32 (m, 1H) 1.36 (d, J=11.37 Hz, 1H) 1.54-1.79 (m, 3H) 1.80-1.96 (m, 2H) 2.06 (br. s., 2H) 2.54-2.64 (m, 1H) 2.97 (br. s., 5H) 3.06-3.27 (m, 2H) 7.14-7.26 (m, 3H) 7.27-7.35 (m, 2H) 9.03 (br. s., 2H) 9.38-9.62 (m, 2H).

Workup

  1. customto give a suspension
  2. custompurified via column chromatography on the ISCO Companion (gradient 0-100% 80:20:2 [CHCl3/MeOH/NH4OH]/CHCl3; 4 g column)
  3. customFractions were collected
  4. customsolvents removed
  5. stirringExcess 2M HCl in Et2O and stirred for 10 minutes
  6. customThe solvent was removed

Sources & evidence

ORD record
ord-4cab5df9166749ad9c86830272d79e51
Source dataset
uspto-grants-2014_10
Patent number
US08853408B2

Reaction notes

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