1,1'-Carbonyldiimidazole → tert-butyl (2S)-2-((3R)-3-((3-chlorophenyl)(2-(ethylamino)-2-oxoethoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

HRID 451884Notes

Reaction equation

HRID 451884 reaction equation
[NH2:1][C@@H:2]([CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C1N=CN([C:25]([N:27]2[CH:31]=N[CH:29]=[CH:28]2)=[O:26])C=1.CCN(C(C)C)C(C)C.[Cl:41][C:42]1[CH:43]=[C:44]([CH:48]([C@@H:56]2CCCN[CH2:57]2)[O:49][CH2:50][C:51]([NH:53][CH2:54][CH3:55])=[O:52])[CH:45]=[CH:46][CH:47]=1>C(Cl)Cl>[Cl:41][C:42]1[CH:43]=[C:44]([CH:48]([O:49][CH2:50][C:51]([NH:53][CH2:54][CH3:55])=[O:52])[C@@H:56]2[CH2:57][CH2:29][CH2:28][N:27]([C:25]([NH:1][C@@H:2]([CH2:13][CH:14]3[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]3)[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:9])([CH3:10])[CH3:8])=[O:26])[CH2:31]2)[CH:45]=[CH:46][CH:47]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 59201313tert-butyl (S)-2-amino-3-cyclohexylpropylmethylcarbamateHCID 592014532-((3-chlorophenyl)((R)-piperidin-3-yl)methoxy)-N-ethylacetamide

Product 1

HCID 59201515tert-butyl (2S)-2-((3R)-3-((3-chlorophenyl)(2-(ethylamino)-2-oxoethoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamateYield 76.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-tert-butyl 2-amino-3-cyclohexylpropyl(methyl)carbamate (34.7 mg, 0.129 mmol) in CH2Cl2 (2 mL) was cooled in an ice-bath and CDI (25 mg, 1.2 mmol) and DIEA (83.2 mg, 0.11 mL, 0.645 mmol) were added. The mixture was stirred at rt for 0.5 h and 2-((3-chlorophenyl)((R)-piperidin-3-yl)methoxy)-N-ethylacetamide (40 mg, 0.129 mmol) was added. The reaction mixture was stirred overnight, washed with brine, dried over Na2SO4 and concentrated to give crude tert-butyl (2S)-2-((3R)-3-((3-chlorophenyl)(2-(ethylamino)-2-oxoethoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate (60 mg, yield: 75.6%). MS (E/Z): 607 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-09dee4b6a1ea420db6295593c6d75f40
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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