Triethylamine → 4-(4-methylpentanoyl)-2-(R)-(2-(R)-acetylamino-1-(S)-hydroxy-3-phenylpropyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1436512Notes

Reaction equation

HRID 1436512 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@@H:9]1[C@@H:14]([OH:27])[C@H:15]([NH:23][C:24](=[O:26])[CH3:25])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:28][CH:29]([CH3:35])[CH2:30][CH2:31][C:32](O)=[O:33].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CN(C1C=CC=CN=1)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:32](=[O:33])[CH2:31][CH2:30][CH:29]([CH3:35])[CH3:28])[CH2:10][C@@H:9]1[C@@H:14]([OH:27])[C@H:15]([NH:23][C:24](=[O:26])[CH3:25])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 12587Isocaproic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 218852-DimethylaminopyridineHCID 757711-HydroxybenzotriazoleHCID 690153032-(R)-(2-(R)-Acetylamino-1-(S)-hydroxy-3-phenyl-propyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 690190384-(4-methylpentanoyl)-2-(R)-(2-(R)-acetylamino-1-(S)-hydroxy-3-phenylpropyl)-piperazine-1-carboxylic acid tert-butyl esterYield 48.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dissolve 2-(R)-(2-(R)-Acetylamino-1-(S)-hydroxy-3-phenyl-propyl)-piperazine-1-carboxylic acid tert-butyl ester (122 mg, 0.32 mmol) in 3 ml of dry CH2Cl2. Add 4-methylpentanoic acid (0.04 ml, 0.32 mmol), EDCI (73.6 mg, 0.38 mmol), HOBT (51.8 mg, 0.38 mmol), triethylamine (0.13 ml, 0.96 mmol) and dimethylaminopyridine (3.9 mg, 0.032 mmol), and stir at room temperature overnight. Dilute with CH2Cl2, and wash with 5% NaHCO3 followed by saturated aqueous sodium chloride. Dry organic layer with MgSO4 and remove the solvent under reduced pressure. Subject residue to silica gel chromatography, eluting with ethyl acetate/methanol 9:1 to obtain 74 mg (48% yield) of a white solid.

Workup

  1. washwash with 5% NaHCO3
  2. customDry organic layer with MgSO4 and remove the solvent under reduced pressure
  3. washSubject residue to silica gel chromatography, eluting with ethyl acetate/methanol 9:1

Sources & evidence

ORD record
ord-c23312a64101455e90e53e3a972f1aa8
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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