Diisopropylamine → ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-3-oxohexanoate

HRID 1967291Notes

Reaction equation

HRID 1967291 reaction equation
C(NC(C)C)(C)C.[C:8]([O:11][CH2:12][CH3:13])(=[O:10])[CH3:9].N1([C:19]([C@@H:21]([NH:24][C:25](=[O:34])[O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:22][CH3:23])=[O:20])C=CN=C1.C(OC(N[C@@H](CC)C(O)=O)=O)C1C=CC=CC=1>O1CCCC1.O.C(O)(=O)C>[CH2:27]([O:26][C:25]([NH:24][C@@H:21]([CH2:22][CH3:23])[C:19](=[O:20])[CH2:9][C:8]([O:11][CH2:12][CH3:13])=[O:10])=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 7349998(2S)-2-(((Phenylmethoxy)carbonyl)amino)butanoic acidHCID 86652877benzyl[(1S)-1-(1H-imidazol-1-ylcarbonyl)propyl]carbamate

Product 1

HCID 67105603ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-3-oxohexanoateYield 57%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diisopropylamine (74.5 mL) in tetrahydrofuran (1 L) was cooled to −78° C., n-butyllithium-hexane solution (329 mL, 1.6 mol/L) was added dropwise, and the mixture was stirred for 1 hr. Ethyl acetate (51.6 mL) was added dropwise and the mixture was stirred at −78° C. for 1 hr. Then, a solution of benzyl [(1S)-1-(1H-imidazol-1-ylcarbonyl)propyl]carbamate prepared from (2S)-2-{[(benzyloxy)carbonyl]amino}butanoic acid (50 g) and N,N′-carbonyldiimidazole (39.5 g) in tetrahydrofuran (300 mL) was added dropwise at −78° C. After stirring at −78° C. for 1 hr, acetic acid was added to the reaction mixture. Water was added and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/0→2/1) to give ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-oxohexanoate as a colorless oil (yield: 36.7 g, 57%).

Workup

  1. additionn-butyllithium-hexane solution (329 mL, 1.6 mol/L) was added dropwise
  2. stirringthe mixture was stirred at −78° C. for 1 hr
  3. additionwas added dropwise at −78° C
  4. stirringAfter stirring at −78° C. for 1 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. dry with materialThe extract was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/0→2/1)

Sources & evidence

ORD record
ord-4eaefd8be6ed46279d823e8f11d37f9c
Source dataset
uspto-grants-2013_04
Patent number
US08420694B2

Reaction notes

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