1,2-Dichloroethane → Phenylmethyl(2R,5S)-2-methyl-5-[(phenylamino)carbonyl]-1-piperidinecarboxylate

HRID 2367414Notes

Reaction equation

HRID 2367414 reaction equation
[CH3:1][C@H:2]1[N:7]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:6][C@@H:5]([C:18]([OH:20])=O)[CH2:4][CH2:3]1.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O>[CH3:1][C@@H:2]1[CH2:3][CH2:4][C@H:5]([C:18]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:20])[CH2:6][N:7]1[C:8]([O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:9]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 6115AnilineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 51357693(3S,6R)-1-((benzyloxy)carbonyl)-6-methylpiperidine-3-carboxylic acid

Product 1

HCID 51357694Phenylmethyl(2R,5S)-2-methyl-5-[(phenylamino)carbonyl]-1-piperidinecarboxylateYield 97.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S,6R)-6-methyl-1-{[(phenylmethyl)oxy]carbonyl}-3-piperidinecarboxylic acid (17 g, 61.3 mmol) in DMF (400 mL) was added aniline (8.56 g, 92 mmol), Hunig's base (32.1 mL, 184 mmol), HOBt (14.08 g, 92 mmol) and EDC (17.63 g, 92 mmol) at room temperature. The reaction mixture was stirred overnight at room temperature, then diluted with H2O (˜100 mL), and extracted with EtOAc (3×250 mL). The combined organic layers were washed with 1N HCl (100 mL), H2O (3×100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the crude title compound (21 g). LC-MS (ES) m/z=353 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×250 mL)
  2. washThe combined organic layers were washed with 1N HCl (100 mL), H2O (3×100 mL), brine (100 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3e34a358ce61436d9eb64936ee3f09f7
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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