Sodium hydride → (R)-tert-butyl 4-benzyl-2-isopropyl-3-oxopiperazine-1-carboxylate

HRID 1482945Notes

Reaction equation

HRID 1482945 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]([CH:22]([CH3:24])[CH3:23])[C:9]([N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:12][CH2:13]Cl)=[O:10])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+]>CN(C=O)C>[CH2:15]([N:11]1[CH2:12][CH2:13][N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:25])[C@H:8]([CH:22]([CH3:24])[CH3:23])[C:9]1=[O:10])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 89827909(R)-tert-butyl(1-(benzyl(2-chloroethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate

Product 1

HCID 89827913(R)-tert-butyl 4-benzyl-2-isopropyl-3-oxopiperazine-1-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-tert-butyl(1-(benzyl(2-chloroethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate (2.0 g, 5.40 mmol) in DMF (30 mL) was added NaH (1.0 g, 27.0 mmol, 60% in oil mineral) at 0° C. under N2. The mixture was stirred at rt for 2 h. The mixture was quenched with water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (20 mL) and dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography to afford (R)-tert-butyl 4-benzyl-2-isopropyl-3-oxopiperazine-1-carboxylate (1.13 g, 63% yield) as a white solid. LC-MS m/z 277.1 [M−56+H]+. 1H NMR (CDCl3 400 MHz): δ 7.38-7.29 (m, 3H), 7.29-7.22 (m, 2H), 5.02-4.86 (m, 1H), 4.49-4.39 (m, 1H), 4.31-4.06 (m, 2H), 3.41-3.18 (m, 3H), 2.42-2.31 (m, 1H), 1.46 (s, 9H), 1.12 (d, J=6.8 Hz, 3H), 1.00 (d, J=6.8 Hz, 3H).

Workup

  1. customThe mixture was quenched with water (20 mL)
  2. extractionextracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with brine (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-67b0593946984b41913d1b523040c48e
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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