Triethylamine → Ethyl N-{4-[{3-([tert-butoxycarbonyl)(methyl)amino]propyl}(methyl)carbamoyl]phenyl}-beta-alaninate

HRID 446603

Reaction equation

HRID 446603 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][CH2:6][NH:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)[CH3:2].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH3:32][N:33]([CH2:41][CH2:42][CH2:43][NH:44][CH3:45])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(OCC)(=O)C>[C:36]([O:35][C:34]([N:33]([CH3:32])[CH2:41][CH2:42][CH2:43][N:44]([CH3:45])[C:12]([C:11]1[CH:10]=[CH:9][C:8]([NH:7][CH2:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:17])=[CH:16][CH:15]=1)=[O:14])=[O:40])([CH3:39])([CH3:38])[CH3:37]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 516892Sodium BicarbonateHCID 17868293tert-butyl N-methyl-N-(3-(methylamino)propyl)carbamateHCID 21830455Ethyl 3-[4-(carboxy)phenylamino]propionate

Product 1

HCID 66793768Ethyl N-{4-[{3-([tert-butoxycarbonyl)(methyl)amino]propyl}(methyl)carbamoyl]phenyl}-beta-alaninateYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-[(3-Ethoxy-3-oxopropyl)amino]benzoic acid (200 mg, 0.84 mmol) (U.S. Pat. No. 5,977,101 A1) was dissolved in methylene chloride (6 mL), triethylamine (0.14 mL, 1.01 mmol) and pivaloyl chloride (0.10 mL, 0.84 mmol) were added under ice cooling, and the mixture was stirred at the same temperature under a nitrogen atmosphere for 15 minutes. Subsequently, a solution of tert-butyl methyl[3-(methylamino)propyl]carbamate (179 mg, 0.89 mmol) in methylene chloride (2 mL) was added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 1:9, v/v) to give the title compound (315 mg; yield, 89%) as a light yellow oily substance.

Workup

  1. stirringthe mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours
  2. customto separate the layers
  3. customThe resulting organic layer was separated
  4. washwashed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 1:9, v/v)

Sources & evidence

ORD record
ord-c58b11a35cee4c7bbece2da914d4954f
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Linked notes

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