2,6-Lutidine → HCID 66782404, compound

HRID 2366330Notes

Reaction equation

HRID 2366330 reaction equation
Cl.[CH3:2][NH:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([O:10][CH3:11])=[O:9].[C:12]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH:18][C:19]([O:21][CH:22]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][C:30](O)=[O:31])[CH2:24][CH2:23]1)=[O:20].ON1C2N=CC=CC=2N=N1.N1C(C)=CC=CC=1C.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO>[CH3:11][O:10][C:8](=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][NH:3][CH2:2][C:30](=[O:31])[CH2:29][CH2:28][N:25]1[CH2:26][CH2:27][CH:22]([O:21][C:19](=[O:20])[NH:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:23][CH2:24]1

Participants

9

Reactant 6

HCID 79372,6-LutidineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic AcidHCID 77231266Methyl 5-(methylamino)pentanoate hydrochloride

Product 1

HCID 66782404HCID 66782404, compoundYield 69.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of methyl 5-methylaminopentanoate hydrochloride (7.27 g, 40.0 mmol), 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (13.3 g, 36.0 mmol) and 1-hydroxy-7-azabenzotriazole (5.14 g, 37.8 mmol) in DCM (160 mL) and 2,6-lutidine (12.5 mL, 108 mmol) was stirred at room temperature for 3 h. N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (10.4 g, 54.0 mmol) was added and the resulting mixture was stirred at room temperature for 2 h. A saturated aqueous sodium bicarbonate solution (˜100 mL) was added and the layers were separated. The aqueous layer was extracted with DCM (50 mL) and the organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (30-100% EtOAc in hexanes; then 2-10% MeOH in DCM) to give the title compound (12.38 g, 69% yield) as a light yellow thick oil/white solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 2 h
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with DCM (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography (30-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-a80b73108407494895b2d9764af5c599
Source dataset
uspto-grants-2014_04
Patent number
US08697724B2

Reaction notes

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