3-Methyl-5-(tributylstannyl)isoxazole → (5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(3-methylisoxazol-5-yl)phenyl)oxazolidin-2-one

HRID 456781Notes

Reaction equation

HRID 456781 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[O:11][C:10]2=[O:20])[CH:5]=[CH:6][C:7]=1I.C([Sn](CCCC)(CCCC)[C:26]1[O:30][N:29]=[C:28]([CH3:31])[CH:27]=1)CCC>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[O:11][C:10]2=[O:20])[CH:5]=[CH:6][C:7]=1[C:26]1[O:30][N:29]=[C:28]([CH3:31])[CH:27]=1

Participants

5

Reactant 2

HCID 27632553-Methyl-5-(tributylstannyl)isoxazoleHCID 11257720(R)-5-((1H-1,2,3-Triazol-1-yl)methyl)-3-(3-fluoro-4-iodophenyl)oxazolidin-2-one2×

Product 1

HCID 9841004(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(3-methylisoxazol-5-yl)phenyl)oxazolidin-2-oneYield 49.7%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

A suspension of (5R)-3-(3-fluoro-4-iodophenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Intermediate 6, 582 mg, 1.50 mmol) in 1,4-dioxane (14 ml) was placed under argon. Bis(triphenylphospine)palladium (II) chloride (42 mg, 0.060 mmol) was added, followed by the dropwise addition of 5-(tributylstannyl)-3-methylisoxazole (Sakamoto, T. et al; Tetrahedron, 1991, 47, 5111–5118; 0.84 g, 2.25 mmol) in 1,4-dioxane (1 ml). The mixture was heated at 100° C. After approximately 16 hours, the solution was concentrated under vacuum. The crude material was dissolved in acetonitrile and washed with hexanes (3×). The acetonitrile phase was concentrated under vacuum. Purification by chromatography on silica gel using EtOAc, followed by recrystallization from EtOAc/MeOH gave 256 mg of the title product.

Workup

  1. concentrationthe solution was concentrated under vacuum
  2. dissolutionThe crude material was dissolved in acetonitrile
  3. washwashed with hexanes (3×)
  4. concentrationThe acetonitrile phase was concentrated under vacuum
  5. customPurification by chromatography on silica gel
  6. customfollowed by recrystallization from EtOAc/MeOH

Sources & evidence

ORD record
ord-09ad8d524771452093dfbf82c20d091e
Source dataset
uspto-grants-2007_03
Patent number
US07186738B2

Reaction notes

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