Tetrahydrofuran → tert-Butyl 4-({[(2-ethoxy-2-oxo-1-pyridin-2-ylethyl)amino]carbonyl} amino)piperidine-1-carboxylate

HRID 1867621Notes

Reaction equation

HRID 1867621 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.C(N(C(C)C)CC)(C)C.[NH2:31][CH:32]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=1)[C:33]([O:35][CH2:36][CH3:37])=[O:34].[O:44]1CCC[CH2:45]1>>[CH2:36]([O:35][C:33](=[O:34])[CH:32]([NH:31][C:45]([NH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=1)[CH3:37]

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 4570669Ethyl 2-amino-2-(pyridin-2-yl)acetate

Product 1

HCID 69054112tert-Butyl 4-({[(2-ethoxy-2-oxo-1-pyridin-2-ylethyl)amino]carbonyl} amino)piperidine-1-carboxylate

Procedure

4-Amino-1-boc-piperidine (302 mg, 1.51 mmol) and triethylamine (0.210 mL, 1.51 mmol) in tetrahydrofuran (5 mL) were added to a solution of p-nitrophenylchloroformate (970 mg, 4.8 mmol) in tetrahydrofuran (15 mL) at 0° C. After 1 h, additional diisopropylethylamine was added (0.420 mL, 3.02 mmol) along with ethyl amino(pyridin-2-yl)acetate (272 mg, 1.51 mmol). The reaction was warmed to room temperature and stirred overnight. The mixture was filtered, concentrated and redissolved in ethyl acetate. The ethyl acetate layer was washed with 1N sodium hydroxide (3×), saturated sodium bicarbonate solution, water, brine, and dried over sodium sulfate. Purification by silica gel chromatography (100% dichloromethane→10% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (330 mg). MS 407.29 (M+1)

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. dissolutionredissolved in ethyl acetate
  4. washThe ethyl acetate layer was washed with 1N sodium hydroxide (3×), saturated sodium bicarbonate solution, water, brine
  5. dry with materialdried over sodium sulfate
  6. customPurification by silica gel chromatography (100% dichloromethane→10% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-0051f8ecb4bd48d1a51537e02649a4de
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

Loading…