Isobutyraldehyde → (2S,3S)-2-((4R)-2-benzhydryl-4-phenyl-oxazolidin-3-yl)-3-hydroxy-4-methyl-pentanoic acid tert-butyl ester

HRID 25683

Reaction equation

HRID 25683 reaction equation
[CH:1]([CH:14]1[N:18]([CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:17]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:16][O:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH:41](=[O:45])[CH:42]([CH3:44])[CH3:43].C(=O)(O)[O-].[Na+]>O1CCCC1>[C:23]([O:22][C:20](=[O:21])[C@@H:19]([N:18]1[C@H:17]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:16][O:15][CH:14]1[CH:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C@@H:41]([OH:45])[CH:42]([CH3:44])[CH3:43])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamideHCID 69754033tert-butyl ((4R)-2-benzhydryl-4-phenyl-oxazolidin-3-yl)-acetate

Product 1

HCID 69752347(2S,3S)-2-((4R)-2-benzhydryl-4-phenyl-oxazolidin-3-yl)-3-hydroxy-4-methyl-pentanoic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of tert-butyl ((4R)-2-benzhydryl-4-phenyl-oxazolidin-3-yl)-acetate (3.0 g, 6.98 mmole, obtained from Reference Example 10) in anhydrous terahydrofuran (86 ml) was cooled at −78° C. under argon. A solution of lithium diisopropylamide (2M solution in heptane/tetrahydrofuran/ethylbenzene, Aldrich) was added dropwise over a period of 10 min, and the resulting orange solution was stirred at −78° C. for 1 h. A solution of isobutyraldehyde in anhydrous tetrahydrofuran (10 ml) was added to the cooled reaction mixture via syringe, and the resulting mixture was stirred at −78° C. for an additional 1 h. Saturated sodium bicarbonate aqueous solution was added, and the mixture was warmed to room temperature. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 times). The extracts were combined, washed with saturated sodium chloride aqueous solution, dried over magnesium sulfate, filtered and concentrated. The residue was chromatographed (flash column, silica gel, methylene chloride:methanol:diethyl ether=90:2:8) to give (2S,3S)-2-((4R)-2-benzhydryl-4-phenyl-oxazolidin-3-yl)-3-hydroxy-4-methyl-pentanoic acid tert-butyl ester (1.5 g, %) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was stirred at −78° C. for an additional 1 h
  2. temperaturethe mixture was warmed to room temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3 times)
  5. washwashed with saturated sodium chloride aqueous solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed (flash column, silica gel, methylene chloride:methanol:diethyl ether=90:2:8)

Sources & evidence

ORD record
ord-8082524e776e4a49acc1e360c46e8567
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Linked notes

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