2,6-Lutidine → HCID 66782404, compound

HRID 1468509Notes

Reaction equation

HRID 1468509 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-1471e9482d9c426ba8a2bf98378e2562
Source dataset
uspto-grants-2015_04
Patent number
US09000173B2

Reaction notes

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