Formaldehyde → tert-Butyl 3,4-dimethylpiperazine-1-carboxylate

HRID 1968103Notes

Reaction equation

HRID 1968103 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]=O>CO.C(O)(=O)C>[CH3:14][CH:10]1[N:11]([CH3:15])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1

Participants

5

Reactant 2

HCID 712FormaldehydeHCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylate

Product 1

HCID 20785237tert-Butyl 3,4-dimethylpiperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl-3-methylpiperazine carboxylate (1.49 g, 7.45 mmol) and paraformaldehyde (1.12 g, 37.2 mmol) were dissolved in a mixture of MeOH and acetic acid (5:1) on molecular sieves. NaBCNH3 (1.88 g, 29.8 mmol) was added to the suspension at 25° C. The slurry was subsequently heated to 80° C. for 10 hr. Then the mixture was cooled, filtered, and concentrated. The residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate. The organic solution was dried over Na2SO4, and concentrated to give a white oily (1.2 g, 90%). LC-MS (ESI) m/z: 215 (M+1)+.

Workup

  1. additionNaBCNH3 (1.88 g, 29.8 mmol) was added to the suspension at 25° C
  2. temperatureThen the mixture was cooled
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed with saturated sodium bicarbonate
  7. dry with materialThe organic solution was dried over Na2SO4
  8. concentrationconcentrated
  9. customto give a white oily (1.2 g, 90%)

Sources & evidence

ORD record
ord-dd11ca0c0d044df2ac46fec70bda9a2b
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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