Diisopropylethylamine → (R)-tert-butyl 4-((1R,2R)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-2-methyl-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 879147Notes

Reaction equation

HRID 879147 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:17])[CH2:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH:27]([C@H:29]1[CH2:33][O:32][C:31]([CH3:35])([CH3:34])[N:30]1[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[O:28]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:17])[C@H:15]([CH3:16])[C@H:27]([C@H:29]1[CH2:33][O:32][C:31]([CH3:35])([CH3:34])[N:30]1[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[OH:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1787923-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)-HCID 10966403(R)-(-)-4-Benzyl-3-propionyl-2-oxazolidinone

Product 1

HCID 11953594(R)-tert-butyl 4-((1R,2R)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-2-methyl-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of (R)-4-benzyl-3-propionyloxazolidin-2-one (1.0 equiv.) in DCM (0.13 M) was added TiCl4 (1.0 equiv.) at −40° C. The mixture was stirred at −40° C. for 10 min (yellow suspension), then DIPEA (2.5 equiv.) was added (dark red solution) and stirred at 0° C. for 20 min. (R)-tert-butyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate (1.0 equiv.) in DCM (0.5 M) was then added dropwise and the resulting mixture was stirred for 1.5 hours. The reaction was quenched by the addition of aqueous ammonium chloride and the mixture was extracted with ethyl acetate. The organic phase was separated, washed with brine, dried with magnesium sulfate, filtered, and concentrated. The residue was purified via column chromatography eluting with ethyl acetate and hexanes (1:4) to give (R)-tert-butyl 4-((1R,2R)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-2-methyl-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate as the major product (5:2) in 58% yield. LC/MS=363.3 (M+H-Boc), Rt=1.09 min.

Workup

  1. additionwas then added dropwise
  2. stirringthe resulting mixture was stirred for 1.5 hours
  3. customThe reaction was quenched by the addition of aqueous ammonium chloride
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified via column chromatography
  11. washeluting with ethyl acetate and hexanes (1:4)

Sources & evidence

ORD record
ord-196d840c21504af5961d36f984698f0c
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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