Sodium Carbonate → (S)-3-(4-(5-Chloropyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525346Notes

Reaction equation

HRID 525346 reaction equation
[CH3:1][C:2]1([CH3:29])[O:6][C:5](=[O:7])[N:4]([C:8]2[CH:13]=[CH:12][C:11](B3OC(C)(C)C(C)(C)O3)=[CH:10][CH:9]=2)[C@H:3]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl[C:31]1[N:32]=[N:33][CH:34]=[C:35]([Cl:37])[CH:36]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:37][C:35]1[CH:36]=[C:31]([C:11]2[CH:12]=[CH:13][C:8]([N:4]3[C@@H:3]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[C:2]([CH3:29])([CH3:1])[O:6][C:5]3=[O:7])=[CH:9][CH:10]=2)[N:32]=[N:33][CH:34]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 199596873,5-DichloropyridazineHCID 89813960(S)-5,5-dimethyl-4-phenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-2-one2×

Product 1

HCID 89813458(S)-3-(4-(5-Chloropyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 25.02%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a 0.5-2.0 mL microwave vial charged with (S)-5,5-dimethyl-4-phenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-2-one (Intermediate J) (0.240 g, 0.610 mmol) and 3,5-dichloropyridazine (commercially available from ACES Pharma, Princeton, N.J.) (0.100 g, 0.671 mmol) were added dioxane (1.220 mL), and 2 M Na2CO3 (1.220 mL). Nitrogen was bubbled through the resulting suspension and then Pd(PPh3)4 (0.071 g, 0.061 mmol) was added. The resulting mixture was irradiated at 100° C. for 30 minutes. LC-MS indicated the formation of product as a major species (two close peaks with product mass, likely isomers) along with other impurities with consumption of starting material. The dark suspension was diluted with water, transferred to a separatory funnel, and extracted with EtOAc (2×). The combined organic layers were dried with Na2SO4, filtered, and dried under reduced pressure. The residual material was purified with a 40 g HP 15 μm spherical silica column (Interchim) ramping EtOAc in heptane from 0-100% leading to isolation of product (primarily one isomer) as the major species with 10-15% impurity. (S)-3-(4-(5-Chloropyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.058 g, 0.153 mmol, 25.02% yield) was obtained as a white solid. Note: the regiochemistry of the product was not confirmed, but it was assumed that the major product would result from the more reactive chloride). m/z (ESI) 380.1 (M+H)+.

Workup

  1. customNitrogen was bubbled through the resulting suspension
  2. customThe resulting mixture was irradiated at 100° C. for 30 minutes
  3. customclose peaks with product mass, likely isomers) along with other impurities
  4. customwith consumption of starting material
  5. additionThe dark suspension was diluted with water
  6. customtransferred to a separatory funnel
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic layers were dried with Na2SO4
  9. filtrationfiltered
  10. customdried under reduced pressure
  11. customThe residual material was purified with a 40 g HP 15 μm spherical silica column (Interchim)

Sources & evidence

ORD record
ord-cd79f83b30cf400e9367d85fbdfece6f
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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