Triethylamine → 1-(3,4-Dichloro-benzyl)-azetidine-3-carbonitrile

HRID 638804Notes

Reaction equation

HRID 638804 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([C:6]#[N:7])[CH2:3]1.C(N(CC)CC)C.[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH2:19]Br>ClCCl>[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH2:19][N:2]1[CH2:5][CH:4]([C:6]#[N:7])[CH2:3]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 45072465Azetidine-3-carbonitrile hydrochloride

Product 1

HCID 687084431-(3,4-Dichloro-benzyl)-azetidine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-Benzhydryl-azetidine-3-carbonitrile (0.25 g, 1.0 mmol) in dichloromethane (2 ml) is treated with 1-chloroethylchloroformate (0.12 ml, 1.1 mmol). The reaction mixture is stirred at room temperature for 3 hours, the solvent evaporated and the residue taken-up in methanol and refluxed for 1 hour. The reaction mixture is cooled to room temperature and stirred for a further 18 hours. The solvent is evaporated to afford crude azetidine-3-carbonitrile hydrochloride. The crude azetidine-3-carbonitrile is dissolved in dichloromethane (3 ml) and treated with triethylamine (0.25 ml, 2.0 mmol) and 3,4-dichlorobenzylbromide (0.24 g, 1.0 mmol). The reaction mixture is stirred at ambient temperature for 2 hours, then washed with water, the organic phase dried over magnesium sulphate and evaporated. The crude product is purified by chromatography over flash silica using hexane:ethylacetate 2:1 as eluent to afford 1-(3,4-Dichloro-benzyl)-azetidine-3-carbonitrile. [MH]+ 240.97

Workup

  1. washwashed with water
  2. dry with materialthe organic phase dried over magnesium sulphate
  3. customevaporated
  4. customThe crude product is purified by chromatography over flash silica

Sources & evidence

ORD record
ord-78544dc24c704182aa3b13509f73b225
Source dataset
uspto-grants-2010_04
Patent number
US07691841B2

Reaction notes

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