Toluene → 4-[[[1-(1,1-Dimethylethoxycarbonyl)-4-piperidinyl]amino]methyl]-3-(ethoxycarbonylamino)-thiophene

HRID 1782697Notes

Reaction equation

HRID 1782697 reaction equation
[CH2:1]([O:3][C:4]([NH:6][C:7]1[C:8]([CH:12]=O)=[CH:9][S:10][CH:11]=1)=[O:5])[CH3:2].[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C1(C)C=CC=CC=1.[BH4-].[Na+]>O>[CH3:26][C:24]([CH3:27])([O:23][C:21]([N:18]1[CH2:17][CH2:16][CH:15]([NH:14][CH2:12][C:8]2[C:7]([NH:6][C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:11][S:10][CH:9]=2)[CH2:20][CH2:19]1)=[O:22])[CH3:25]

Participants

6

Reactant 4

HCID 1140TolueneHCID 12682914-Amino-1-Boc-piperidineHCID 4311764Sodium borohydrideHCID 146721634-(Ethoxycarbonylamino)-thiophene-3-carboxaldehyde

Product 1

HCID 183215714-[[[1-(1,1-Dimethylethoxycarbonyl)-4-piperidinyl]amino]methyl]-3-(ethoxycarbonylamino)-thiophene

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 28.2 g (0.142 mol) of 4-(ethoxycarbonyl-amino)-thiophene-3-carboxaldehyde, 28.2 g (0.141 mol) of 4-amino-1-(1,1-dimethyl-ethoxycarbonyl)piperidine and 300 ml of toluene was refluxed using a water separator until water formation had ceased. The solvent was removed in vacuo, the residue was dissolved in 300 ml of methanol and at room temperature combined batchwise with 5.5 g (0.145 mol) of sodium borohydride. The mixture was stirred for a further hour at room temperature, then evaporated down in vacuo and the residue was distributed between water and tert. butyl-methylether. The organic phase was dried over sodium sulphate and freed from solvent in vacuo. The oily residue was further processed without purification.

Workup

  1. temperaturewas refluxed
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in 300 ml of methanol and at room temperature
  4. customevaporated down in vacuo
  5. dry with materialThe organic phase was dried over sodium sulphate
  6. customThe oily residue was further processed without purification

Sources & evidence

ORD record
ord-2bc2df2cc74f40edba51ff4f322dc1db
Source dataset
uspto-grants-2009_03
Patent number
US07498325B2

Reaction notes

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