ChemicalBook CAS DataBase List 5-FLUORO-2-HYDROXYMETHYL PYRIDINE

5-FLUORO-2-HYDROXYMETHYL PYRIDINE synthesis

4synthesis methods

Product Name:5-FLUORO-2-HYDROXYMETHYL PYRIDINE
CAS Number:802325-29-7
Molecular formula:C6H6FNO
Molecular Weight:127.12

107504-08-5
266 suppliers
$7.00/250mg

802325-29-7
94 suppliers
$50.00/250mg

Yield: 52%

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 0; for 12 h;Inert atmosphere;

Steps:

67
A mixture of 14 (500 mg, 4 mmol) and LiAIH₄(202 mg, 5 mmol) in THF (10 mL) was degassed and purged with N₂for 3 times, and then the mixture was stirred at 0 °C for 12 h under N₂atmosphere. The reaction mixture was quenched by saturated sodium potassium tartrate (0.8 mL) at 15 °C, and then filtered. The mixture was diluted with H₂0 (5 mL) and extracted with EtOAc (5 mL x 3). The combined organic layer was washed with brine (5 mL x 2), dried over Na₂S0₄, filtered and concentrated under reduced pressure to give 15 (236 mg, 52%) as a yellow solid.¹H NMR (400 MHz, DMSO-d₆) 8.43 (d, J - 2.8 Hz, 1 H), 7.45-7.41 (m, 1 H), 7.31-7.27 (m, 1 H), 4.76 (s, 2H). A mixture of 15 (1 g, 8 mmol), DCC (3 g, 16 mmol), DMAP (96 mg, 786 umol) and A/-BOC-(S)-valine (2 g, 9 mmol) in DCM (5 mL) was degassed and purged with N₂for 3 times, and then the mixture was stirred at 25 "C for 12 h under N₂atmosphere. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Si0₂, PE/EtOAc = 5:1) to give 16 (1 .3 g, 51 %) as a yellow liquid.¹H N R (400 MHz, DMSO-de) 8.55 (s, 1 H), 7.71-7.83 (m, 1 H), 7.54-7.51 (m, 1 H), 7.25 (d, J = 8.0 Hz, 1 H), 5.22-5.13 (m, 2H), 3.91 (t, J = 7.2 Hz, 1 H), 2.06-2.02 (m, 1 H), 1.38 (s, 9H), 0.87 (d, J - 6.4 Hz, 6H).

References:

ANACOR PHARMACEUTICALS, INC.;AKAMA, Tsutomu;CARTER, David Scott;HALLADAY, Jason S.;JACOBS, Robert T.;LIU, Yang;PLATTNER, Jacob J.;ZHANG, Yong-Kang;WITTY, Michael John WO2017/195069, 2017, A1 Location in patent:Page/Page column 61