2,6-Lutidine → (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-chloropyrimidin-4-yl)oxazolidin-2-one

HRID 57350Notes

Reaction equation

HRID 57350 reaction equation
[C:1]([O:5][C@@H:6]([CH3:18])[C@H:7]([NH:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]([Cl:17])[N:12]=1)[CH2:8][OH:9])([CH3:4])([CH3:3])[CH3:2].Cl[C:20](Cl)([O:22]C(=O)OC(Cl)(Cl)Cl)Cl.CC1C=CC=C(C)N=1.CCOC(C)=O.CCCCCCC>C(Cl)Cl.O>[C:1]([O:5][C@H:6]([C@H:7]1[CH2:8][O:9][C:20](=[O:22])[N:10]1[C:11]1[CH:16]=[CH:15][N:14]=[C:13]([Cl:17])[N:12]=1)[CH3:18])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 94429TriphosgeneHCID 21899848Ethylacetate heptaneHCID 90417085(2R,3S)-3-(tert-butoxy)-2-((2-chloropyrimidin-4-yl)amino)butan-1-ol

Product 1

HCID 90414526(R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-chloropyrimidin-4-yl)oxazolidin-2-oneYield 132.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a round bottom flask containing (2R,3S)-3-(tert-butoxy)-2-((2-chloropyrimidin-4-yl)amino)butan-1-ol (1.8 g, 6.58 mmol) and a stir bar under nitrogen was added DCM (66 ml). The resulting reaction mixture cooled to −70° C. in a dry ice/acetone bath. To this cold solution was added triphosgene (1.07 g, 3.62 mmol) followed by the addition of 2,6-dimethylpyridine (3.6 mL, 30.9 mmol). Resulting reaction mixture allowed to gradually warm to room temperature and stirred for 30 min at room temperature. Reaction mixture diluted with DCM and water and allowed to stir 1 hr at room temperature. The phases were then partioned and aqueous extracted with DCM. Organics phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-chloropyrimidin-4-yl)oxazolidin-2-one (1.44 g, 4.80 mmol, 73% yield) as a white crystalline. LCMS m/z 300.1 (M+H)+, Rt 0.91 min.

Workup

  1. customThe resulting reaction mixture
  2. customResulting
  3. customreaction mixture
  4. temperatureto gradually warm to room temperature
  5. customReaction mixture
  6. stirringto stir 1 hr at room temperature
  7. extractionaqueous extracted with DCM
  8. washwashed with water, brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-7c8ed31fa2a5495a9110442833a50b0c
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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