2-Bromopyridine → HCID 69939689, compound

HRID 1058301Notes

Reaction equation

HRID 1058301 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[CH2:13]([C@@H:20]1[CH2:24][O:23][C:22](=[O:25])[N:21]1[C:26](=[O:42])/[CH:27]=[CH:28]/[C:29]1[CH:30]=[C:31]([CH:39]=[CH:40][CH:41]=1)[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1.CSC>[CH2:13]([C@@H:20]1[CH2:24][O:23][C:22](=[O:25])[N:21]1[C:26](=[O:42])[CH2:27][C@H:28]([C:29]1[CH:30]=[C:31]([CH:39]=[CH:40][CH:41]=1)[C:32]([O:34][C:35]([CH3:37])([CH3:38])[CH3:36])=[O:33])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 69937937HCID 69937937, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 69939689HCID 69939689, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 1068Dimethyl SulfideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a 1.0 M solution of isopropylmagnesium chloride (1.0 mL, 2.08 mmol) in THF was added 2-bromopyridine (0.198 mL, 2.08 mmol) and the mixture was stirred for 1.5 hours. This dark solution, at 0° C., was quickly added to a cooled (−40° C.) solution of CuBr.DMS complex (0.206 g, 1.01 mmol) in THF (2 mL) and dimethylsulfide (1 mL), and the resulting mixture was stirred at −40° C. for 10 min, then placed in an ice bath. Tert-butyl 3-{(1E)-3-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxoprop-1-enyl}benzoate from the previous step, dissolved in THF (2 mL), was added dropwise and the mixture was stirred for 1.5 hours. The reaction was quenched with 20% aqueous NH4Cl solution, the dimethylsulfide was removed under reduced pressure and the mixture was partitioned between EtOAc and H2O. The layers were separated, the water layer was extracted with EtOAc, and the combined organics were washed with H2O and brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on a 10 g ISCO column using 0-40% EtOAc/hexanes over 40 min. The lower diastereomer was combined to give tert-butyl 3-{(1R)-3-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxo-1-pyridin-2-ylpropyl}benzoate as an oil (0.12 g, 37%). Absolute chirality was assigned based on literature precedent. TLC Rf=0.3 (1:1 EtOAc:hexanes, UV visualization); HPLC RT=2.1 min, method B; M+H=488.

Workup

  1. additionThis dark solution, at 0° C., was quickly added to
  2. customplaced in an ice bath
  3. additionwas added dropwise
  4. stirringthe mixture was stirred for 1.5 hours
  5. customThe reaction was quenched with 20% aqueous NH4Cl solution
  6. customthe dimethylsulfide was removed under reduced pressure
  7. customthe mixture was partitioned between EtOAc and H2O
  8. customThe layers were separated
  9. extractionthe water layer was extracted with EtOAc
  10. washthe combined organics were washed with H2O and brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customthe solvent was removed under reduced pressure
  14. customThe residue was chromatographed on a 10 g ISCO column
  15. customover 40 min

Sources & evidence

ORD record
ord-d516065b2b7d4c66bfcd5f243a04749f
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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