Sodium hydride → HCID 86739940, compound

HRID 615857Notes

Reaction equation

HRID 615857 reaction equation
[H-].[Na+].Br[CH2:4][C:5]([O:7][CH3:8])=[O:6].[N:9]([C@H:12]1[C@@H:15]([CH2:16][OH:17])[N:14]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:13]1=[O:26])=[N+:10]=[N-:11]>CN(C)C=O>[N:9]([C@H:12]1[C@@H:15]([CH2:16][O:17][CH2:4][C:5]([O:7][CH3:8])=[O:6])[N:14]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:13]1=[O:26])=[N+:10]=[N-:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 86739938HCID 86739938, compound

Product 1

HCID 86739940HCID 86739940, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-20 °C

Procedure

A suspension of 60% sodium hydride (749 mg, 18.72 mmole) was washed under argon with hexane (9 ml). The sodium hydride was then cooled to -20° C. and dimethylformamide (20 ml) was added. The mixture was then cooled to -50° C. and methyl bromoacetate (1.77 ml, 18.72 mmole) was added via syringe. Next, a solution of (±)-(cis)-3-azido-4-hydroxymethyl-1-(4-methoxyphenyl)-2-oxoazetidine (3.303 g, 13.37 mmole) in dimethylformamide (25 ml) was added dropwise. The reaction was stirred at -50° C. for ten minutes, warmed to -20° C. over 40 minutes, stirred at this temperature for thirty minutes, and then stirred at -5° C. overnight (ca. sixteen hours). The solvent was mostly removed in vacuo (30° C.). The residue was treated with ether, then pH 4.5 monobasic potassium phosphate buffer. The aqueous layer was extracted with additional ether. The organic extracts were washed with cold 0.5 N hydrochloric acid, water, brine, dried (sodium sulfate), and filtered and concentrated to 4.2 g of an orange oil. The crude product was chromatographed on silica gel (180 g, 230-400 mesh) eluting with 60% hexane-ethyl acetate. Combination of fractions 35-46 (20 ml fractions), concentration and drying in vacuo produced 2.46 g of the title compond as an oil.

Workup

  1. washwas washed under argon with hexane (9 ml)
  2. additiondimethylformamide (20 ml) was added
  3. temperatureThe mixture was then cooled to -50° C.
  4. temperaturewarmed to -20° C. over 40 minutes
  5. stirringstirred at this temperature for thirty minutes
  6. stirringstirred at -5° C. overnight (ca. sixteen hours)
  7. customThe solvent was mostly removed in vacuo (30° C.)
  8. additionThe residue was treated with ether
  9. extractionThe aqueous layer was extracted with additional ether
  10. washThe organic extracts were washed with cold 0.5 N hydrochloric acid, water, brine
  11. dry with materialdried (sodium sulfate)
  12. filtrationfiltered
  13. concentrationconcentrated to 4.2 g of an orange oil
  14. customThe crude product was chromatographed on silica gel (180 g, 230-400 mesh)
  15. washeluting with 60% hexane-ethyl acetate
  16. concentrationCombination of fractions 35-46 (20 ml fractions), concentration
  17. customdrying in vacuo
  18. customproduced 2.46 g of the title compond as an oil

Sources & evidence

ORD record
ord-b80cb41d25704b3493b697a452f787b5
Source dataset
uspto-grants-1985_02
Patent number
US04501697

Reaction notes

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