Hydrochloric Acid → HCID 86751035, compound

HRID 1602582Notes

Reaction equation

HRID 1602582 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:23][CH2:24][CH3:25])(=[O:22])[C@H:14]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[OH:15].Br[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].Cl>CCCCCC.O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[OH:15][C@H:14]([C:13]([O:23][CH2:24][CH3:25])=[O:22])[C@H:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 79177tert-Butyl bromoacetateHCID 1715085Diethyl L-malateHCID 178418339Butyllithium

Product 1

HCID 86751035HCID 86751035, compoundYield 48.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-78 °C

Procedure

31 ml of 1.69M n-butyllithium in hexane was dissolved in 30 ml of tetrahydrofuran, and 7.1 ml of diisopropylamine was added under cooling with ice. The resulting solution was stirred at the same temperature for 30 minutes at then cooled to -78° C. 4.94 g of diethyl (S)-malate in 20 ml of tetrahydrofuran was added dropwise at -50° C. or below, and the reaction solution was stirred at -20° C. for 1.5 hours. The reaction solution was cooled to -78° C., and a solution of 5.58 g of tert-butyl bromoacetate and 4.66 g of hexamethylphosphoric triamide in 20 ml of tetrahydrofuran was added dropwise at -50° C. or below. Then, the reaction solution was stirred at room temperature for 1 hour. The reaction solution was poured into 150 ml of 0.5N hydrochloric acid and extracted with diethyl ether, and the organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography [hexane/ethyl acetate=5/1→4/1] to give 3.8 g of the title compound as a yellow oily substance.

Workup

  1. temperatureunder cooling with ice
  2. stirringthe reaction solution was stirred at -20° C. for 1.5 hours
  3. temperatureThe reaction solution was cooled to -78° C.
  4. stirringThen, the reaction solution was stirred at room temperature for 1 hour
  5. extractionextracted with diethyl ether
  6. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe desiccant was filtered off
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe residue was purified by silica gel column chromatography [hexane/ethyl acetate=5/1→4/1]

Sources & evidence

ORD record
ord-46ea21c617a84cdabbd735fd8923462d
Source dataset
uspto-grants-1999_11
Patent number
US05981573

Reaction notes

Loading…