2-Bromo-5-hydroxypyridine → Thiazole

HRID 1746131Notes

Reaction equation

HRID 1746131 reaction equation
[O:1]1[CH:5]=[CH:4][CH2:3][NH:2]1.Br[C:7]1[N:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1.C([Sn](CCCC)(CCCC)[C:19]1[S:20][CH:21]=[CH:22][N:23]=1)CCC>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:12]1[CH:7]=[CH:8][CH:9]=[C:10]([O:13][C:3]2[CH2:4][CH2:5][O:1][N:2]=2)[CH:11]=1.[S:20]1[CH:21]=[CH:22][N:23]=[CH:19]1

Participants

7

Reactant 3

HCID 27628652-Bromo-5-hydroxypyridineHCID 27632592-(Tributylstannyl)-1,3-thiazoleHCID 193504172,3-Dihydro-1,2-oxazole

Product 2

HCID 9256ThiazoleHCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-162a and I-162b were prepared according to the following procedure: Racemic dihydroisoxazole I-161 was prepared in 1 step from compound I-14 and 6-bromopyridin-3-ol using Method 5. Compound I-161 placed in a microwave vial and then dissolved in dioxane (0.02 M). 2-(tributylstannyl)thiazole and palladium tetrakis were added and the reaction was purged with Argon. At this point the reaction was heated in the microwave reactor for 20 min after which there was no starting material by TLC analysis. The mixture is concentrated and purified by flash silica gel chromatography (hexanes/ethyl acetate) to provide the desired racemic thiazole I-162 in 50% yield. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M−H]−=407.3 m/z. Activity: A

Workup

  1. customthe reaction was purged with Argon
  2. temperatureAt this point the reaction was heated in the microwave reactor for 20 min after which there
  3. concentrationThe mixture is concentrated
  4. custompurified by flash silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-07360885a76f4d7e9592a7094c958e0a
Source dataset
uspto-grants-2015_10
Patent number
US09149465B2

Reaction notes

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