tert-Butyl piperazine-1-carboxylate → 1-Piperazinecarboxylic acid, 4-[[5-chloro-2-(4-morpholinyl)phenyl]methyl]-, 1,1-dimethylethyl ester

HRID 2278223Notes

Reaction equation

HRID 2278223 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:6]([CH:9]=1)[CH:7]=O.[N:16]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:6]([CH2:7][N:19]2[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20]2)[CH:9]=1

Participants

5

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 89677169HCID 89677169, compound

Product 1

HCID 896771271-Piperazinecarboxylic acid, 4-[[5-chloro-2-(4-morpholinyl)phenyl]methyl]-, 1,1-dimethylethyl esterYield 113.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A round-bottom flask was charged with 5-chloro-2-(morpholin-4-yl)benzaldehyde (1.60 g, 7.09 mmol, 1.00 equiv), tert-butyl piperazine-1-carboxylate (1.20 g, 6.43 mmol, 0.910 equiv), 1,2-dichloromethane (20 mL). The mixture was stirred at room temperature for 0.5 hour. Sodium triacetoxyborohydride (4.09 g, 19.3 mmol, 2.72 equiv) was added. The resulting solution was stirred overnight at room temperature and diluted with H2O (50 mL). The resulting solution was extracted with dichloromethane (2×20 mL), the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/4) to yield 2.90 g (crude) of tert-butyl 4-[[5-chloro-2-(morpholin-4-yl)phenyl]methyl]piperazine-1-carboxylate as yellow oil. LCMS (ESI, m/z): 396 [M+H]+.

Workup

  1. stirringThe resulting solution was stirred overnight at room temperature
  2. extractionThe resulting solution was extracted with dichloromethane (2×20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/4)

Sources & evidence

ORD record
ord-f38175d57a6745f9b9a2096d6cddc522
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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