Formaldehyde → 4-(t-Butoxycarbonyl)-1-methylpiperazine-2-carboxamide

HRID 13773Notes

Reaction equation

HRID 13773 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([C:14]([NH2:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.[C:19](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH3:19])[CH:10]([C:14]([NH2:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 11042527Tert-butyl 3-carbamoylpiperazine-1-carboxylate

Product 1

HCID 231459204-(t-Butoxycarbonyl)-1-methylpiperazine-2-carboxamideYield 85.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 6.00 g of 4-(t-butoxycarbonyl)piperazine-2-carboxamide and 3.28 g of a 37% aqueous formaldehyde solution in 60 ml of methanol was ice-cooled, and 16.66 g of sodium triacetoxyborohydride was added, followed by stirring at room temperature for 24 hours after removing an ice bath. The reaction solution was again ice-cooled, 3.28 g of a 37% aqueous formaldehyde solution and 16.66 g of sodium triacetoxyborohydride were added thereto. After stirring at room temperature for 16 hours, the reaction solution was diluted with ice water, alkalified with an aqueous saturated sodium hydrogen carbonate solution, followed by extraction with ethyl acetate three times. The organic layers were combined and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 5.42 g of the objective compound as colorless crystals.

Workup

  1. temperaturecooled
  2. customafter removing an ice bath
  3. temperaturecooled
  4. addition3.28 g of a 37% aqueous formaldehyde solution and 16.66 g of sodium triacetoxyborohydride were added
  5. stirringAfter stirring at room temperature for 16 hours
  6. additionthe reaction solution was diluted with ice water
  7. extractionfollowed by extraction with ethyl acetate three times
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e507ba266287468784932d4566153100
Source dataset
uspto-grants-2010_06
Patent number
US07728131B2

Reaction notes

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