Formaldehyde → 1,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@@H:11]([CH3:22])[CH2:10]2)=[CH:4][CH:3]=1.[CH2:23]=O.C[O-].[Na+].[BH4-].[Na+]>CO.CC(C)=O>[CH3:22][C@H:11]1[CH2:10][N:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([NH:1][CH3:23])=[CH:3][CH:4]=2)[CH2:14][CH2:13][N:12]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
A mixture of 1,1-dimethylethyl (2S)-4-[(4-aminophenyl)methyl]-2-methyl-1-piperazinecarboxylate (D22) (7.45 g, 24.43 mmol), paraformaldehyde (2.202 g, 73.28 mmol) and sodium methoxide (6.597 g, 122.13 mmol) in MeOH (150 mL) under an argon atmosphere was heated at 50° C. over-weekend. After cooling, sodium borohydride (1.848 g, 48.85 mmol) was added and the reaction mixture was heated at 50° C. for 1 h then cooled to room temperature. Acetone was added until no more bubbling was observed, then the mixture was concentrated. The residue was partitioned between DCM and water and the aqueous was re-extracted with DCM. The combined organics were diluted with MeOH (approx 20 mL) to aid solubility, dried and concentrated to yield the title compound as an off white solid (7.77 g)
Workup
- temperatureAfter cooling
- temperaturethe reaction mixture was heated at 50° C. for 1 h
- temperaturethen cooled to room temperature
- customno more bubbling
- concentrationthe mixture was concentrated
- customThe residue was partitioned between DCM and water
- extractionthe aqueous was re-extracted with DCM
- additionThe combined organics were diluted with MeOH (approx 20 mL)
- customdried
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-1ba91d565950454f9540694219a12c38
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08012981B2
Reaction notes
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