Dichloromethane → HCID 90415010, compound

HRID 57344Notes

Reaction equation

HRID 57344 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([C@H:13]([OH:15])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[C:4]([Cl:17])[N:3]=1.[CH2:18](Cl)Cl.F[B-](F)(F)F.[H+].C[Si](C=[N+]=[N-])(C)C>CCOC(C)=O.CCCCCCC>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([C@H:13]([O:15][CH3:18])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[C:4]([Cl:17])[N:3]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 28118Tetrafluoroboric acidHCID 167693Trimethylsilyldiazomethane2×HCID 90415074(R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one

Product 1

HCID 90415010HCID 90415010, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 21899848Ethylacetate heptaneSolvent

Procedure

To a round bottom flask was added (R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one (364 mg, 1.31 mmol) followed by the addition of DCM (10.8 mL). The reaction mixture was then cooled to 0° C. in a (ice/water bath) under nitrogen. To this cold solution was added tetrafluoroboric acid (0.20 mL, 1.31 mmol, 50% aqueous solution) followed by the addition of trimethylsilyldiazomethane (1.96 mL, 3.93 mmol, 2 M in hexanes) divided into 3 portions added 20 min apart. A second addition of trimethylsilyldiazomethane in hexanes (1.96 mL, 3.93 mmol, 2 M in hexanes) again divided into 3 portions added 20 min apart was added. Reaction mixture was quenched with water and diluted with DCM. Phases paritioned and the aqueous phase extracted with DCM. Organic phases combined and washed with brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-3-(2,6-dichloropyrimidin-4-yl)-4-((R)-1-methoxyethyl)oxazolidin-2-one (119 mg, 0.41 mmol, 31% yield) as a colorless oil which crystallizes upon standing. 1H NMR (400 MHz, CDCl3) δ 1.09 (d, J=6.50 Hz, 3H) 3.44 (s, 3H) 4.09 (qd, J=6.46, 4.16 Hz, 1H) 4.38-4.49 (m, 1H) 4.60 (dd, J=9.49, 2.84 Hz, 1H) 4.99 (ddd, J=8.50, 3.95, 2.96 Hz, 1H) 8.23 (s, 1H). LCMS m/z 292.0 (M+H)+, Rt 0.86 min.

Workup

  1. additionadded 20 min apart
  2. additionadded 20 min
  3. additionapart was added
  4. customReaction mixture
  5. customwas quenched with water
  6. additiondiluted with DCM
  7. extractionthe aqueous phase extracted with DCM
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-60d426bf7b9c40ac8767f2f2717be8ee
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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