Chemical Properties
Light Brown Solid
Uses
(2-Amino-3-chlorophenyl)methanol is a useful reactant in the synthesis of CGRP-receptor antagonists and PI3K inhibitors.
Synthesis
The general procedure for the synthesis of (2-amino-3-chlorophenyl)methanol from 2-amino-3-chlorobenzoic acid is as follows:
1. a solution of lithium aluminum hydride (210 mL, 1 M, 210 mmol) in tetrahydrofuran (THF) was cooled to room temperature under nitrogen protection.
2. A solution of 2-amino-3-chlorobenzoic acid (15.0 g, 87.4 mmol) in THF (200 mL) was added slowly for a controlled dosing time of 20 minutes.
3. After the addition was completed, the reaction mixture was continued to be stirred at room temperature for 1.5 hours.
4. The reaction mixture was cooled to 10 °C and water (300 mL) was slowly added to quench the reaction.
5. The resulting suspension was filtered through a diatomaceous earth pad which was well rinsed with ethyl acetate (EtOAc, 1 L).
6. The filtrates were combined, washed with saturated saline (3 × 300 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to afford the target product (2-amino-3-chlorophenyl)methanol (2a) (13.0 g, 94% yield).
Product characterization: 1H NMR (500 MHz, CDCl3) δ 4.69 (s, 2H), 6.63 (t, J = 5.2 Hz, 1H), 6.97 (d, J = 5.0 Hz, 1H), 7.24 (d, J = 5.0 Hz, 1H).
References
[1] Patent: US2006/211705, 2006, A1. Location in patent: Page/Page column 33
[2] Patent: US2007/219370, 2007, A1. Location in patent: Page/Page column 24; 25
[3] Tetrahedron Letters, 2017, vol. 58, # 40, p. 3795 - 3799
[4] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 19, p. 5810 - 5831
[5] Patent: US2010/29598, 2010, A1. Location in patent: Page/Page column 19-20
