Acetic Anhydride → 4-{3-[4-(3-Hydroxypropyl)-1-piperidinyl]propoxy}benzamidine

HRID 644128Notes

Reaction equation

HRID 644128 reaction equation
O[N:2]=[C:3]([NH2:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][CH2:22][OH:23])[CH2:16][CH2:15]2)=[CH:6][CH:5]=1.C(OC(=O)C)(=O)C>[C].[Pd].C(O)(=O)C>[OH:23][CH2:22][CH2:21][CH2:20][CH:17]1[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([NH2:24])=[NH:2])=[CH:5][CH:6]=2)[CH2:15][CH2:16]1

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 72264642N'-hydroxy-4-{3-[4-(3-hydroxypropyl)-1-piperidinyl]propoxy}benzamidine

Product 1

HCID 592630234-{3-[4-(3-Hydroxypropyl)-1-piperidinyl]propoxy}benzamidineYield 88.5%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 176Acetic AcidSolvent

Procedure

To an acetic acid (80 mL) suspension of 10.0 g of N′-hydroxy-4-{3-[4-(3-hydroxypropyl)-1-piperidinyl]propoxy}benzamidine were added 5.31 mL of acetic anhydride and 0.50 g of 5% palladium-carbon at room temperature, which was stirred at room temperature under hydrogen atmosphere for 12 hours and 50 minutes. After filtering off insoluble matter, the solvent was distilled off under reduced pressure. To the resultant residue was added 6 mol/L hydrochloric acid, followed by distilling off the solvent under reduced pressure before purification using silica gel column chromatography (silica gel: ODS-A from YMC, eluent; water). The eluate was concentrated to about 100 mL under reduced pressure and then adjusted to pH 12 using a 5 mol/L sodium hydroxide aqueous solution. The precipitate was collected by filtration and washed with water to provide 8.43 g of 4-{3-[4-(3-hydroxypropyl)-1-piperidinyl]propoxy}benzamidine as white solid form.

Workup

  1. filtrationAfter filtering off insoluble matter
  2. distillationthe solvent was distilled off under reduced pressure
  3. additionTo the resultant residue was added 6 mol/L hydrochloric acid
  4. distillationby distilling off the solvent under reduced pressure
  5. custombefore purification
  6. concentrationThe eluate was concentrated to about 100 mL under reduced pressure
  7. filtrationThe precipitate was collected by filtration
  8. washwashed with water

Sources & evidence

ORD record
ord-d5b7758db0a2460fbb34c46d3d28969b
Source dataset
uspto-grants-2010_04
Patent number
US07700623B2

Reaction notes

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