Lithium Hydroxide → 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

HRID 1614994Notes

Reaction equation

HRID 1614994 reaction equation
Br[C:2]1[CH2:6][CH2:5][O:4][N:3]=1.COC(=O)[C:10]1[CH:15]=[C:14]([OH:16])[CH:13]=[N:12][CH:11]=1.[OH-].[Li+].O1CCCC1>O1CCCC1.O>[N:12]1[CH:11]=[CH:10][CH:15]=[C:14]([O:16][C:2]2[CH2:6][CH2:5][O:4][N:3]=2)[CH:13]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 354317Methyl 5-hydroxypyridine-3-carboxylateHCID 219834983-Bromo-4,5-dihydroisoxazole

Product 1

HCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

The enantiomers of 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole III-74a and III-74b were prepared in 2 steps according to the following procedures: racemic 3-bromo 4,5-dihydroisoxazole III-66 was reacted with 5-hydroxynicotinic acid methyl ester using Method 5. The resulting ester (1.0 equiv) was dissolved in 1:1 tetrahydrofuran/water (0.06 M) and lithium hydroxide (8.0 equiv) was added. The reaction was allowed to stir at room temperature for 1 h after which point the tetrahydrofuran was removed under a stream of nitrogen and the remaining solution was acidified to pH<2 with 1N HCl to provide the racemic desired acid III-74 as a white solid which was isolated via vacuum filtration. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=395.5 m/z. Activity: A

Workup

  1. additionwas added
  2. customwas removed under a stream of nitrogen

Sources & evidence

ORD record
ord-f320e0728bc8497ab9a6ddbc698743d9
Source dataset
uspto-grants-2014_07
Patent number
US08765735B2

Reaction notes

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