Lithium Hydroxide → (2S)-4-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-3-methyl-4-oxobutanoic acid

HRID 1424214Notes

Reaction equation

HRID 1424214 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:22]([O:24]C)=[O:23])[CH:10]([CH3:21])[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>C1COCC1.O>[CH2:14]([O:13][C:11](=[O:12])[CH:10]([CH3:21])[C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C:22]([OH:24])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 866991284-benzyl 1-methyl N-(tert-butoxycarbonyl)-3-methyl-L-aspartate

Product 1

HCID 86699113(2S)-4-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-3-methyl-4-oxobutanoic acidYield 38%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of 4-benzyl 1-methyl N-(tert-butoxycarbonyl)-3-methyl-L-aspartate (Preparation 68, 0.5 g, 1.52 mmol) in THF/water (50 mL/10 mL) was added lithium hydroxide (34 mg, 1.42 mmol) at 0° C. and the reaction stirred warming slowly to room temperature for 18 hours. The reaction was extracted with heptane and the aqueous was acidified with 10% aqueous KHSO4 solution. The solution was extracted with EtOAc, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified using reverse phase column chromatography eluting with 0-60% MeCN in 0.1% formic acid in water to afford the title compound (182 mg, 38%).

Workup

  1. extractionThe reaction was extracted with heptane
  2. extractionThe solution was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified
  7. washeluting with 0-60% MeCN in 0.1% formic acid in water

Sources & evidence

ORD record
ord-31db73615b5b496d869f4b30613c1f88
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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