Hydrochloric Acid → 1-Benzyl-4-(1,3-dihydroxyprop-2-ylamino)-piperidine

HRID 352431Notes

Reaction equation

HRID 352431 reaction equation
[NH2:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4].[CH2:7]([N:14]1[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.[OH-].[Na+]>C(Cl)Cl.O>[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([NH:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4])[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 68294SerinolHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 227120471-Benzyl-4-(1,3-dihydroxyprop-2-ylamino)-piperidineYield 91.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

2.75 g of 2-aminopropane-1,3-diol and 5.9 g of 1-benzyl-4-piperidone are dissolved in 60 ml of methylene chloride and a total of 9.9 g of sodium triacetoxyborohydride are added batchwise while cooling with ice. The mixture is left to stand overnight at ambient temperature. 60 ml of methylene chloride and some water are added, then conc. hydrochloric acid is added while cooling with ice until an acidic reaction is obtained. The mixture is stirred for about another 15 min. while cooling and then made significantly alkaline with 4 N sodium hydroxide solution. The aqueous phase is separated off, the organic phase is washed with a very little water, dried over sodium sulphate and the solvent is eliminated in vacuo. 8 g of substance are obtained which are chromatographed with methylene chloride/methanol 8:2 over 150 g of silica gel. The fractions found to be uniform by TLC are combined and the solvent is eliminated in vacuo. 7.3 g of 1-benzyl-4-(1,3-dihydroxyprop-2-ylamino)-piperdine are obtained.

Workup

  1. temperaturewhile cooling with ice
  2. waitThe mixture is left
  3. temperaturewhile cooling with ice until an acidic reaction
  4. customis obtained
  5. temperaturewhile cooling
  6. customThe aqueous phase is separated off
  7. washthe organic phase is washed with a very little water
  8. dry with materialdried over sodium sulphate
  9. custom8 g of substance are obtained which
  10. customare chromatographed with methylene chloride/methanol 8:2 over 150 g of silica gel

Sources & evidence

ORD record
ord-f7a939ceea6a46beb41993a57990e445
Source dataset
uspto-grants-2004_06
Patent number
US06747044B2

Reaction notes

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