Sodium borohydride → HCID 56947739, compound

HRID 572830Notes

Reaction equation

HRID 572830 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]([CH:11]([O:21][CH:22]2[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]2)[C:12]2[S:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[N:16]=2)[CH:8]=[CH:9][CH:10]=1)C=C.[BH4-].[Na+]>O1CCCC1.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>[S:13]1[C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[N:16]=[C:12]1[CH:11]([O:21][CH:22]1[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]1)[C:7]1[CH:6]=[C:5]([OH:4])[CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 66835982HCID 66835982, compound

Product 1

HCID 56947739HCID 56947739, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[(3-allyloxyphenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole (example 22) (2.35 g) in tetrahydrofurane (40 mL) is added tetrakistriphenylphosphinepalladium (0.344 g). The mixture is stirred for 5 min at room temperature, then sodium borohydride (0.576 g) is added. The mixture is stirred for 20 h at room temperature, filtered over a clarcel pad. The pad is rinsed with ethyl acetate. Pooled organic phases are washed with aqueous ammonium chloride solution, then sodium hydrogenocarbonate, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by three column chromatographies over silica gel (twice gradient heptane/ethyl acetate from 95/5 to 80/20, third eluant heptane/dichloromethane 5/1). Pooled fractions are concentrated under reduced pressure. The residue is dissolved in methanol, refluxed for 5 h and concentrated under reduced pressure. The residue is purified by column chromatography (gradient dichloromethane/methanol/ammonia from 100/0 to 90/10/1) to give 3-[benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenol as a beige solid melting at 201° C.

Workup

  1. stirringThe mixture is stirred for 20 h at room temperature
  2. filtrationfiltered over a clarcel pad
  3. washThe pad is rinsed with ethyl acetate
  4. washPooled organic phases are washed with aqueous ammonium chloride solution
  5. dry with materialsodium hydrogenocarbonate, dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by three column chromatographies over silica gel (twice gradient heptane/ethyl acetate from 95/5 to 80/20, third eluant heptane/dichloromethane 5/1)
  8. concentrationPooled fractions are concentrated under reduced pressure
  9. dissolutionThe residue is dissolved in methanol
  10. temperaturerefluxed for 5 h
  11. concentrationconcentrated under reduced pressure
  12. customThe residue is purified by column chromatography (gradient dichloromethane/methanol/ammonia from 100/0 to 90/10/1)

Sources & evidence

ORD record
ord-5b0f3fb512284eb38c117ba2ad068079
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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