Triethylamine → N-[(S)-1-Carbethoxybutyl]-(S)-alanine Benzyl Ester

HRID 2112282Notes

Reaction equation

HRID 2112282 reaction equation
C([NH:3][C@H:4]([C:8]([O-:10])=[O:9])[CH2:5][CH2:6][CH3:7])C.[CH2:11]([O:18][C:19](=[O:23])[C@H:20](Br)[CH3:21])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH2:24](N(CC)CC)[CH3:25]>C(#N)C.C(OC(C)C)(C)C.O>[CH2:11]([O:18][C:19](=[O:23])[C@H:20]([CH3:21])[NH:3][C@H:4]([C:8]([O:10][CH2:24][CH3:25])=[O:9])[CH2:5][CH2:6][CH3:7])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 86609522ethyl-L-norvalinateHCID 86609523benzyl-(R)-2-bromo-propionate

Product 1

HCID 11493275N-[(S)-1-Carbethoxybutyl]-(S)-alanine Benzyl EsterYield 407.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 7914Diisopropyl EtherSolvent

Procedure

To a solution of ethyl-L-norvalinate (IV, 62 g, 0.427 moles) in acetonitrile (300 ml) were added successively benzyl-(R)-2-bromo-propionate (V1, 20 g, 0.0822 moles) and triethyl amine (28 ml, 0.2016 moles). The reaction mixture was refluxed for 7-8 hrs. The excess solvent was removed by distillation under reduced pressure to afford a thick oil. The oil was dissolved in a mixture of diisopropyl ether (80 ml) and water (40 ml). The organic phase was extracted in 10% hydrochloric acid solution (40 ml×2). The combined acidic extracts were made alkaline by addition of an aqueous solution of sodium carbonate. The aqueous phase was again extracted with diisopropyl ether (200 ml×2). The combined organic layer was concentrated under reduced pressure to afford 103 g of the title compound as an oil.

Workup

  1. temperatureThe reaction mixture was refluxed for 7-8 hrs
  2. customThe excess solvent was removed by distillation under reduced pressure
  3. customto afford a thick oil
  4. extractionThe organic phase was extracted in 10% hydrochloric acid solution (40 ml×2)
  5. additionby addition of an aqueous solution of sodium carbonate
  6. extractionThe aqueous phase was again extracted with diisopropyl ether (200 ml×2)
  7. concentrationThe combined organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-7e99a1d774494b0ca4ef0e889f3258f3
Source dataset
uspto-grants-2009_04
Patent number
US07521566B2

Reaction notes

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