3-Hydroxypyridine → Oxalate

HRID 572881Notes

Reaction equation

HRID 572881 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1.CC(C)([C:29](=[O:37])CC(=O)C(C)(C)C)C.[C:39](=[O:42])([O-:41])[O-].[Cs+].[Cs+].[OH:45][C:46]1[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=1>CC(C)=O.[Cu]I.CN(C)C=O>[CH3:25][N:22]1[CH2:23][CH2:24][CH:19]([O:18][CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([O:45][C:46]3[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=3)[CH:3]=2)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH2:20][CH2:21]1.[C:29]([O-:37])(=[O:18])[C:39]([O-:41])=[O:42]

Participants

9

Reactant 4

HCID 79713-HydroxypyridineHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 569474582-[(3-Iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole

Product 2

HCID 71081OxalateHCID 668357042-{(1-Methylpiperidin-4-yloxy)[3-(pyridin-3-yloxy)phenyl]methyl}benzothiazole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 180AcetoneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A screw-capped tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole (example 41, 500 mg), copper(I) iodide (9 mg), 2,2,6,6-tetramethylheptane-3,5-dione (37 mg), cesium carbonate (701 mg), 3-hydroxypyridine (125 mg), powdered 4A molecular sieves (200 mg) and anhydrous N,N-dimethylformamide (1 mL). The tube is evacuated, filled with argon and sealed. After stirring at 95° C. for 2 days, the mixture is diluted with ethyl acetate, water and ammonia. After decantation, the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5). to afford the pure base that is then converted into its oxalate salt in acetone to give 2-{(1-methylpiperidin-4-yloxy)[3-(pyridin-3-yloxy)phenyl]methyl}benzothiazole, oxalate melting at 78° C.

Workup

  1. customThe tube is evacuated
  2. additionfilled with argon
  3. customsealed
  4. additionthe mixture is diluted with ethyl acetate, water and ammonia
  5. extractionAfter decantation, the aqueous phase is extracted with ethyl acetate
  6. dry with materialThe pooled organic extracts are dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)
  9. customto afford the pure base that

Sources & evidence

ORD record
ord-87d063111d3d48d2b6065c69802fb903
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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