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

HRID 1167581Notes

Reaction equation

HRID 1167581 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-aminopropan-1,3-diol and 5.9 g of 1-benzyl-4-piperidone are dissolved in 60 ml of methylene chloride and while cooling with ice a total of 9.9 g of sodium triacetoxyborohydride are added batchwise. 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 acid reaction is obtained. The mixture is stirred for about another 15 min. with cooling and then made clearly 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 freed from solvent in vacuo. 8 g of substance are obtained which are chromatographed with methylene chloride/methanol 8:2 over 150 g of silica gel. The uniform fractions according to TLC are combined and freed from solvent in vacuo. 7.3 g of 1-benzyl-4-(1,3-dihydroxyprop-2-ylamino)-piperidine are obtained.

Workup

  1. additionare added batchwise
  2. waitThe mixture is left
  3. temperaturewhile cooling with ice until an acid reaction
  4. customis obtained
  5. temperaturewith 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-39caeb2870554280be5c78a95ecbd6f3
Source dataset
uspto-grants-2003_09
Patent number
US06620438B2

Reaction notes

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