Water → 6-((S)-3-Methyl-piperazin-1-yl)-nicotinic acid ethyl ester

HRID 42205Notes

Reaction equation

HRID 42205 reaction equation
C(N(CC)CC)C.[CH2:8]([O:10][C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15](Cl)=[N:14][CH:13]=1)[CH3:9].[CH3:20][C@H:21]1[CH2:26][NH:25][CH2:24][CH2:23][NH:22]1.O>CN1C(=O)CCC1.CCOC(C)=O>[CH2:8]([O:10][C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15]([N:25]2[CH2:24][CH2:23][NH:22][C@@H:21]([CH3:20])[CH2:26]2)=[N:14][CH:13]=1)[CH3:9]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 27342192-Methylpiperazine, (S)-HCID 2799611Ethyl 6-chloronicotinate

Product 1

HCID 574716156-((S)-3-Methyl-piperazin-1-yl)-nicotinic acid ethyl esterYield 52%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Triethylamine (3.7 mL, 27 mmol, 5.0 eq) is added to a solution of 6-chloronicotinic acid ethyl ester (1.0 g, 5.4 mmol, 1 eq), (S)-2-methyl-piperazine (540 mg, 5.4 mmol, 1 eq) in NMP (6 mL) in a microwave vial. The vial is sealed and irradiated in the microwave at 150° C. (high absorption setting) for 30 min. Water (15 mL) and EtOAc (100 mL) are added, the organic layer is separated, dried over sodium sulfate and concentrated under reduced pressure to a white residue. The desired compound is isolated by silica gel chromatography (5-60% EtOAc/Heptane, then 10% MeOH/Heptane), (700 mg, 52% yield).

Workup

  1. customThe vial is sealed
  2. customirradiated in the microwave at 150° C. (high absorption setting) for 30 min
  3. customthe organic layer is separated
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure to a white residue

Sources & evidence

ORD record
ord-ff17e2b0b0b7402f81388c5f8b9d5c17
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Reaction notes

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