Ammonium Chloride → dimethyl (R)-N-tert-butoxycarbonyl-3-acetylaspartate

HRID 1493382Notes

Reaction equation

HRID 1493382 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:13][C:14]([NH:16][C@@H:17]([C:23]([O:25][CH3:26])=[O:24])[CH2:18][C:19]([O:21][CH3:22])=[O:20])=[O:15])([CH3:12])([CH3:11])[CH3:10].[C:27](C1NC=CN=1)(=[O:29])[CH3:28].[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[C:9]([O:13][C:14]([NH:16][C@@H:17]([C:23]([O:25][CH3:26])=[O:24])[CH:18]([C:27](=[O:29])[CH3:28])[C:19]([O:21][CH3:22])=[O:20])=[O:15])([CH3:11])([CH3:12])[CH3:10]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 5389722-AcetylimidazoleHCID 2724682Lithium diisopropylamideHCID 15092456(R)-Dimethyl 2-(tert-butoxycarbonylamino)succinate

Product 1

HCID 15092460dimethyl (R)-N-tert-butoxycarbonyl-3-acetylaspartateYield 38.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of lithium diisopropylamide (30.8%, 10.5 ml, 22 m mol) in hexane was added to a solution of dimethyl (R)-N-tert-butoxycarbonylaspartate (2.61 g, 10 m mol) in tetrahydrofuran (50 ml) at -78° C. in a stream of nitrogen and the mixture was stirred for 10 minutes at -78° C. After stirring for 20 minutes at -40° C., the reaction mixture was again cooled to -78° C., to which a solution of acetylimidazole (1.32 g, 12 m mol) in tetrahydrofuran (15 ml) was added dropwise. After stirring the reaction mixture for 10 minutes, a saturated ammonium chloride solution was added and the resulting mixture was stirred at room temperature. The resultant was diluted with water and extracted with ethyl acetate. The organic layer was washed with a saturated NaCl solution, dried over sodium sulfate and distilled off under reduced pressure to remove the solvent. The residue was subjected to a silica gel column chromatography (2.5×40 cm; ethyl acetate: hexane=1:3) to obtain dimethyl (R)-N-tert-butoxycarbonyl-3-acetylaspartate (1.16 g, 38%) as colorless oil.

Workup

  1. stirringAfter stirring for 20 minutes at -40° C.
  2. additionwas added dropwise
  3. stirringAfter stirring the reaction mixture for 10 minutes
  4. stirringthe resulting mixture was stirred at room temperature
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with a saturated NaCl solution
  7. dry with materialdried over sodium sulfate
  8. distillationdistilled off under reduced pressure
  9. customto remove the solvent

Sources & evidence

ORD record
ord-c620a4b7d47147a3ba5b6d70eb6bf9ac
Source dataset
uspto-grants-1991_06
Patent number
US05021439

Reaction notes

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