N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → (S)-3-tert-Butoxycarbonylamino-1-[4-({[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]ethylamino}methyl)piperidin-1-yl]-propan-1-one

HRID 429831Notes

Reaction equation

HRID 429831 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:14]1[C:18]2[CH:19]=[CH:20][C:21]([CH2:23][C@@H:24]([N:26]([CH2:29][CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[CH2:27][CH3:28])[CH3:25])=[CH:22][C:17]=2[CH2:16][CH2:15]1>ClCCl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([N:33]1[CH2:34][CH2:35][CH:30]([CH2:29][N:26]([C@@H:24]([CH3:25])[CH2:23][C:21]2[CH:20]=[CH:19][C:18]3[O:14][CH2:15][CH2:16][C:17]=3[CH:22]=2)[CH2:27][CH3:28])[CH2:31][CH2:32]1)=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 15546287(S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(piperidin-4-ylmethyl)amine

Product 1

HCID 54233503(S)-3-tert-Butoxycarbonylamino-1-[4-({[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]ethylamino}methyl)piperidin-1-yl]-propan-1-oneYield 97.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-tert-butoxycarbonyl-β-alanine (0.31 grams, 165 mmole) in dichloromethane (5 ml) was added N,N′-carbonyldiimidazole (0.3 grams, 185 mmole). The reaction mixture was stirred at room temperature for 2 hours. To the reaction mixture was added a solution of (S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(piperidine-4-ylmethyl)amine (0.5 grams, 1.65 mmole) in dichloromethane (2 ml). The reaction mixture was stirred for 16 hours. The solvent was evaporated and the residue was purified by flash chromatography on silica gel using 2% methanol in dichloromethane containing 0.1% ammonium hydroxide. Appropriate fractions were combined and concentrated to give (S)-3-tert-butoxycarbonylamino-1-[4-({[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-ethylamino}methyl)piperidin-1-yl]propan-1-one as a solid (0.76 grams, 97%).

Workup

  1. stirringThe reaction mixture was stirred for 16 hours
  2. customThe solvent was evaporated
  3. customthe residue was purified by flash chromatography on silica gel using 2% methanol in dichloromethane containing 0.1% ammonium hydroxide
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-5ca099bd3998408abc74940048be0e87
Source dataset
uspto-grants-2001_11
Patent number
US06319920B1

Reaction notes

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