(4S)-4-[(1R)-1-carboxy-but-3-enyl]-2,2-dimethyl-1,3-dioxolan-5-one → (2R)-N-[(1S)-1-[(benzyloxy)carbonyl]-2,2-dimethylpropyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]pent-4-enamide

HRID 1701012Notes

Reaction equation

HRID 1701012 reaction equation
[C:1]([C@@H:4]([C@H:8]1[C:12](=[O:13])[O:11][C:10]([CH3:15])([CH3:14])[O:9]1)[CH2:5][CH:6]=[CH2:7])([OH:3])=O.Cl.[CH2:17]([O:24][C:25](=[O:32])[C@H:26]([C:28]([CH3:31])([CH3:30])[CH3:29])[NH2:27])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:24][C:25]([C@@H:26]([NH:27][C:1](=[O:3])[C@@H:4]([C@H:8]1[C:12](=[O:13])[O:11][C:10]([CH3:15])([CH3:14])[O:9]1)[CH2:5][CH:6]=[CH2:7])[C:28]([CH3:30])([CH3:29])[CH3:31])=[O:32])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

3

Reactant 2

HCID 59875758(4S)-4-[(1R)-1-carboxy-but-3-enyl]-2,2-dimethyl-1,3-dioxolan-5-oneHCID 71758258benzyl (2S)-2-amino-3,3-dimethylbutanoate hydrochloride

Product 1

HCID 59875749(2R)-N-[(1S)-1-[(benzyloxy)carbonyl]-2,2-dimethylpropyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]pent-4-enamideYield 87%

Procedure

According to the method of Preparation 2, (4S)-4-[(1R)-1-carboxy-but-3-enyl]-2,2-dimethyl-1,3-dioxolan-5-one (Preparation 14b)(2.39 g, 11.20 mmol) was reacted with L-tert-leucine benzyl ester hydrochloride (3.03 g, 11.76 mmol) for 1 h at 4° C. and then 17 h at 20° C. The mixture was concentrated under reduced pressure, dissolved in ethyl acetate (200 mL), washed with 0.5M aqueous sodium dihydrogenphosphate (2×200 mL), 5% saturated sodium bicarbonate (200 mL), water, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate 10:1 to 1:1) to give (2R)-N-[(1S)-1-[(benzyloxy)carbonyl]-2,2-dimethylpropyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]pent-4-enamide (4.06 g, 87%), as a white solid.

Workup

  1. custom17 h
  2. customat 20° C
  3. concentrationThe mixture was concentrated under reduced pressure
  4. dissolutiondissolved in ethyl acetate (200 mL)
  5. washwashed with 0.5M aqueous sodium dihydrogenphosphate (2×200 mL), 5% saturated sodium bicarbonate (200 mL), water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (gradient elution with hexane:ethyl acetate 10:1 to 1:1)

Sources & evidence

ORD record
ord-30013680e4a54c01a22a9dfdad72c1e9
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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