Sodium Iodide → Benzyl 4-(pyrimidin-4-yl-methyl)piperazine-1-carboxylate

HRID 1804624Notes

Reaction equation

HRID 1804624 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH2:8])=[N:3][CH:2]=1.Cl[CH2:10][CH2:11][N:12]([CH2:23][CH2:24]Cl)[C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)C(C)C)(C)C.[I-].[Na+]>COCCOCCOC.C(OCC)C.CO>[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[CH2:24][CH2:23][N:12]([C:13]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:22])[CH2:11][CH2:10]2)=[N:3][CH:2]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 12553191N-Cbz-N,N-bis(2-chloroethyl)amineHCID 12933348Pyrimidin-4-ylmethanamine

Product 1

HCID 67518105Benzyl 4-(pyrimidin-4-yl-methyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8150DiglymeSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of 0.20 g (1.8 mmol) of 1-(pyrimidin-4-yl)methanamine and 0.61 g (2.2 mmol) benzyl bis(2-chloroethyl)carbamate in 4 mL anhydrous diethylene glycol dimethyl ether was added 3.20 mL (18.3 mmol) of N,N-diisopropylethylamine and 0.05 g (0.40 mmol) of sodium iodide. The resulting solution was heated to 150° C. for 6 h. After cooling to ambient temperature, 12 mL of methanol was added to the mixture followed by 250 mL of diethyl ether. The resulting white precipitate was isolated by vacuum filtration while washing with diethyl ether. Diluted the solid with 100 mL of saturated sodium bicarbonate and extracted the aqueous solution with ethyl acetate (3×100 mL). The combined organic layers were dried with magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as a white solid which was used without further purification. LC/MS: m/z (ES) 313.1 (MH)+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customThe resulting white precipitate was isolated by vacuum filtration
  3. washwhile washing with diethyl ether
  4. additionDiluted the solid with 100 mL of saturated sodium bicarbonate
  5. extractionextracted the aqueous solution with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic layers were dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-52c75e2032164ab58ad9587b37402e48
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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