Diisopropylethylamine → 2-methyl-2-(4-oxetan-3-yl-piperazin-1-yl)-propionaldehyde

HRID 1778450Notes

Reaction equation

HRID 1778450 reaction equation
Br[C:2]([CH3:6])([CH3:5])[CH:3]=[O:4].[O:7]1[CH2:10][CH:9]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH2:8]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:5][C:2]([N:14]1[CH2:15][CH2:16][N:11]([CH:9]2[CH2:10][O:7][CH2:8]2)[CH2:12][CH2:13]1)([CH3:6])[CH:3]=[O:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5783772-Bromo-2-methylpropanalHCID 574162871-(Oxetan-3-yl)piperazine

Product 1

HCID 900015642-methyl-2-(4-oxetan-3-yl-piperazin-1-yl)-propionaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-bromo-2-methyl-propanal (696.6 mg, 4.61 mmol) in DCM (10 mL) was cooled with an ice bath and 1-(oxetan-3-yl)piperazine (328 mg, 2.31 mmol), diluted with 5-10 mL of DCM, was slowly added via addition funnel over a 15 min period. Next, Hunig's base (0.4 mL, 2.31 mmol) was added and then the cooling bath was removed. The reaction mixture was stirred at room temperature overnight and the DCM layer was washed three times with 0.5N HCl. The combined aqueous layer was neutralized with NaOH to pH 10-11 and extracted with DCM. The combined organic layer was washed with brine and dried over Na2SO4. Filtration and removal of solvent afforded 2-methyl-2-[4-(oxetan-3-yl)piperazin-1-yl]propanal as a light yellow liquid, which was used directly in the next step without further purification.

Workup

  1. additionwas slowly added via addition funnel over a 15 min period
  2. customthe cooling bath was removed
  3. washthe DCM layer was washed three times with 0.5N HCl
  4. extractionextracted with DCM
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationFiltration and removal of solvent

Sources & evidence

ORD record
ord-b9dfc139285e425082aa195e3bd7bde7
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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