Triethylamine → (S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-ester

HRID 42190

Reaction equation

HRID 42190 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([C:12]([F:15])([F:14])[F:13])=[N:7][C:8](Cl)=[N:9][CH:10]=1)=[O:4].[CH3:16][O:17][C:18]([C@H:20]1[NH:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1)=[O:19].C(N(CC)CC)C>O1CCOCC1>[CH3:16][O:17][C:18]([C@H:20]1[N:25]([C:8]2[N:7]=[C:6]([C:12]([F:15])([F:14])[F:13])[C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][N:9]=2)[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1)=[O:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 15018551-tert-butyl 3-methyl (3S)-piperazine-1,3-dicarboxylateHCID 3696469Methyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

Product 1

HCID 68707290(S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-esterYield 61%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine 2-Chloro-4-trifluoromethyl-pyrimidine-5-carboxylic acid methyl ester (240 mg, 1.70 mmol), (S)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (2.04 mmol) and triethylamine (5.11 mmol) in a 0.85 M solution of dioxane. Microwave reaction mixture for 30 min at 150° C. Filter reaction mixture and rinse with acetonitrile. Purify filtrate by column chromatography in a 0-70% ethyl acetate/heptane gradient to give (S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-ester contaminated with approximately 15% of the mono hydrolysis product. The mixture is carried on to next step without further purification. (61% yield)

Workup

  1. customMicrowave reaction mixture for 30 min at 150° C
  2. filtrationFilter
  3. customreaction mixture
  4. washrinse with acetonitrile

Sources & evidence

ORD record
ord-eb9edd583b6146c588dccfa774168ab9
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Linked notes

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