4-Methylmorpholine → [2-(1-Carbamoyl-3-methyl-butylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester

HRID 1593991Notes

Reaction equation

HRID 1593991 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[C:18]([OH:20])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:22][C@H:23]([C:28]([NH2:30])=[O:29])[CH2:24][CH:25]([CH3:27])[CH3:26].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C.O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[C:18](=[O:20])[NH:22][CH:23]([C:28](=[O:29])[NH2:30])[CH2:24][CH:25]([CH3:27])[CH3:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733199Leucinamide hydrochlorideHCID 125126072-(((Benzyloxy)carbonyl)amino)cyclohexane-1-carboxylic acid

Product 1

HCID 20732578[2-(1-Carbamoyl-3-methyl-butylcarbamoyl)-cyclohexyl]-carbamic acid benzyl esterYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the carboxylic acid of step 2 (10.2 g, 36.9 mmol), L-Leucineamide hydrochloride (6.18 g, 40.5 mmol), EDCI hydrochloride (5.48 g, 40.6 mmol), and HOBT (5.48 g, 40.6 mmol) in 100 mL of anhydrous DMF, was added N-methylmorpholine (12.0 mL, 109 mmol). The reaction mixture was stirred at ambient temperature for 24 h, then added 300 mL of water and 400 mL of ethyl acetate. The organic layer was separated and washed with two 300 mL portions of a 0.5 M HCl solution, 300 mL of water, then dried over sodium sulfate, filtered and recrystallized from ethyl acetate/hexanes to give 13.2 g of [2-(1-Carbamoyl-3-methyl-butylcarbamoyl)-cyclohexyl]-carbamic acid benzyl ester as a white solid. Yield: 92%, MS: 412 (M+Na+), mp=188.0-189.5° C.

Workup

  1. customThe organic layer was separated
  2. washwashed with two 300 mL portions of a 0.5 M HCl solution, 300 mL of water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customrecrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-95405e0e563a469eb3166cb1f21fa5ae
Source dataset
uspto-grants-2007_11
Patent number
US07300934B2

Reaction notes

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