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A process for preparing (S)-1-(3-hydroxypiperidin-1-yl)prop-2-en-1-one

IP.com Disclosure Number: IPCOM000236571D
Publication Date: 2014-May-04
Document File: 1 page(s) / 11K

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A process for preparing (S)-1-(3-hydroxypiperidin-1-yl)prop-2-en-1-one

     Provided herein is a process for preparing (S)-1-(3-hydroxypiperidin-1- yl)prop-2-en-1-one, referred herein as Compound I. The process is described in Example 1.

Compound I may be used for preparing (S)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H- pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.

Example 1: A process for preparing (S)-1-(3-hydroxypiperidin-1-yl)prop-2-en-1- one

    Flask (4 L) equipped with overhead stirrer, thermometer and dropping funnel was charged with (S)-3-hydroxypiperidine HCl (100 g, 0.727 mol). Solution of K2CO3 (301.3 g, 2.18 mol, 3 eq.) in water (272 mL) was added. Water (300 mL) was added to complete dissolution of starting compound. Ethyl acetate (1000 mL) was added and the resulting two phase system was cooled to -15 °C. Acryloyl chloride (64.9 mL, 72.4 g, 0.799 mol,
1.1 eq.) in ethyl acetate (200 mL) was added dropwise to the vigorously stirred mixture within 80 min. The temperature didn't exceed -10 °C. HPLC-MS showed complete conversion after additional 30 min. A solution of 0.1 M 4-methoxyphenol (9.1 mL) was added and the mixture was left to reach room temperature. The phases were separated and aqueous phase was re-extracted with ethyl acetate (3×500 mL). The combined organic extracts were dried over Na2SO4 concentrated at 30 °C to ca 85 mL of remaining ethyl acetate. Cyclohexane (100 mL) was added under cooling in ice bath, grinding with glass stirring...