1,3-Propanediol → Oxalate

HRID 572855Notes

Reaction equation

HRID 572855 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.CC1C=NC2C(C=1C)=CC=C1C=2N=CC(C)=C1C.[C:44](=[O:47])([O-:46])[O-].[Cs+].[Cs+].[CH2:50]([OH:54])[CH2:51][CH2:52][OH:53]>[Cu]I.C1(C)C=CC=CC=1>[S:10]1[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=[C:9]1[CH:8]([O:18][CH:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1)[C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[O:53][CH2:52][CH2:51][CH2:50][OH:54].[C:19]([O-:18])(=[O:53])[C:44]([O-:46])=[O:47]

Participants

8

Reactant 4

HCID 104421,3-PropanediolHCID 10796Cesium carbonateHCID 742653,4,7,8-Tetramethyl-1,10-phenanthrolineHCID 569474582-[(3-Iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole

Product 2

HCID 71081OxalateHCID 668359593-{3-[Benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenoxy}propan-1-ol

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A screw-capped tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole (example 41, 150 mg), copper(I) iodide (6.5 mg), 3,4,7,8-tetramethyl-1,10-phenanthroline (16.3 mg), cesium carbonate (223 mg), propan-1,3-diol (74 mg), ground 4 Å molecular sieves (80 mg) and toluene (4 mL). The tube is evacuated, filled with argon and sealed. After stirring at 90° C. for 24 h, the mixture is diluted with dichloromethane, water and ammonia. After filtration and decantation, the aqueous phase is extracted with dichloromethane. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5). The base is converted into its oxalate salt in acetone to give 3-{3-[benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenoxy}propan-1-ol, oxalate melting at 79° C.

Workup

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

Sources & evidence

ORD record
ord-179e085c0e9e48a8989718f0408544a9
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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