1-(aminomethyl)cyclopentanol hydrochloride synthesis

Yield:76066-27-8 68%

Reaction Conditions:

Stage #1:1-hydroxycyclopentanecarbonitrile with lithium aluminium tetrahydride in tetrahydrofuran at 0; for 1 h;Reflux;
Stage #2: with hydrogenchloride in 1,4-dioxane;tert-butyl methyl ether at 20; for 0.5 h;

Steps:

100.1 Step 1: 1-(Aminomethyl)cyclopentanol hydrochloride
To an ice cooled mixture of cyclopentanone (5.50 g, 65.0 mmol) and ZnBr₂ (0.20 g, 8.00 mmol) was added TMSCN (10.0 mL, 73.4 mmol) and stirred at room temperature for 12 hours. The resulting cyanohydrin solution was added dropwise to a suspension of LiAlH₄ (8.34 g, 219 mmol) in THF (30.0 mL) at 0° C. and mixture was refluxed for 1 hour. The reaction mixture was cooled to room temperature, water (10.0 mL), 4 M aqueous NaOH solution (10.0 mL) followed by water (10.0 mL) was added slowly to the reaction mixture with vigorous stirring. The resultant precipitate was filtered through a pad of celite, the organic phase separated and dried over KOH. The solution was decanted, dried (Na₂SO₄), filtered and concentrated. The residue was dissolved in MTBE (100 mL), 4N HCl in dioxane (10.0 mL) was added and mixture was stirred at room temperature for 30 minutes. The resulting precipitate was collected by filtering through sintered funnel to provide product (6.68 g, 68%) as a white solid.

References:

Merck Sharp & Dohme Corp.;Merck Canada Inc.;McCauley, John A.;Bennett, David Jonathan;Bungard, Christopher J.;Greshock, Thomas J.;Holloway, M. Katharine;Williams, Peter D.;Beaulieu, Christian;Crane, Sheldon;Lessard, Stephanie;Mckay, Daniel;Molinaro, Carmela;Moradei, Oscar Miguel;Sivalenka, Vijayasaradhi;Truong, Vouy Linh;Tummanapalli, Satyanarayana US2017/217986, 2017, A1 Location in patent:Paragraph 0564; 0565

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