6-Chloropyridine-2-carbonitrile → 1-(6-Chloropyridin-2-yl)cyclopropan-1-amine

HRID 1040478Notes

Reaction equation

HRID 1040478 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][CH:3]=1.[CH2:10]([Mg]Br)[CH3:11]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2([NH2:9])[CH2:11][CH2:10]2)[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 1184246-Chloropyridine-2-carbonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 552646581-(6-Chloropyridin-2-yl)cyclopropan-1-amineYield 14.1%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-Chloro-pyridine-2-carbonitrile (500 mg, 3.61 mmol) in THF (45 mL) was added titanium isopropoxide (1.59 mL, 5.41 mmol) in one portion followed by ethylmagnesium bromide (3 M in Et2O, 3.6 mL, 11 mmol) slowly over 5 min. The reaction was stirred for 4 then quenched by the addition of water (5 mL). The mixture was filtered through a pad of diatomaceous earth and the filtrate was concentrated. The resulting material was purified first by flash chromatography (silica, 5→10% MeOH/CH2Cl2) and then by reversed phase HPLC (1→95% MeCN/H2O+0.1% TFA) to give 86 mg of the title compound presumably as the bis-TFA salt, m/z 169.59 [M+1]+.

Workup

  1. customthen quenched by the addition of water (5 mL)
  2. filtrationThe mixture was filtered through a pad of diatomaceous earth
  3. concentrationthe filtrate was concentrated
  4. customThe resulting material was purified first by flash chromatography (silica, 5→10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-6627a78109a44490bf6d1cf558b1288c
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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