Tris(furan-2-yl)phosphane → N-((5-(4-((4S,5R)-3-(2,2-dichloroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methyl)-ethanesulfonamide

HRID 1520454Notes

Reaction equation

HRID 1520454 reaction equation
[Cl:1][CH:2]([Cl:24])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([Sn](C)(C)C)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:23])[CH3:22])=[O:4].Br[C:26]1[CH:27]=[CH:28][C:29]([CH2:32][NH:33][S:34]([CH2:37][CH3:38])(=[O:36])=[O:35])=[N:30][CH:31]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>CN1CCCC1=O.C(OC(=O)C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][CH:2]([Cl:24])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:26]3[CH:27]=[CH:28][C:29]([CH2:32][NH:33][S:34]([CH2:37][CH3:38])(=[O:35])=[O:36])=[N:30][CH:31]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:23])[CH3:22])=[O:4]

Participants

7

Reactant 3

HCID 521585Tris(furan-2-yl)phosphaneHCID 86695409HCID 86695409, compoundHCID 866954112,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(trimethylstannyl)-phenyl)-oxazolidin-3-yl)ethanone

Product 1

HCID 86695410N-((5-(4-((4S,5R)-3-(2,2-dichloroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methyl)-ethanesulfonamideYield 43.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

2,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(trimethylstannyl)-phenyl)-oxazolidin-3-yl)ethanone (281 mg, 0.66 mmol) and N-((5-bromopyridin-2-yl)methyl)ethanesulfonamide (155 mg, 0.56 mmol) are dissolved in N-Methyl-2-pyrrolidone (40 mL) and purged with nitrogen gas. Pd2(dba)3 (51 mg, 0.055 mmol) and tri-2-furylphosphine (27 mg, 0.11 mmol) are added; the resulting mixture is heated to 80° C. for 18 hours. The reaction mixture is cooled, diluted with ethylacetate, and washed with water. The organic phase is dried (Na2SO4) and concentrated under vacuum. The crude material is chromatographed (24 g Redi-Sep column) eluting from 100% hexanes to 90:10 ethylacetate:hexanes to afford the title compound (125 mg): m/z (Cl) M+H 518.

Workup

  1. custompurged with nitrogen gas
  2. temperatureThe reaction mixture is cooled
  3. washwashed with water
  4. dry with materialThe organic phase is dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customThe crude material is chromatographed (24 g Redi-Sep column)
  7. washeluting from 100% hexanes to 90:10 ethylacetate

Sources & evidence

ORD record
ord-d6d5d3c8bc58430b9ed3feb98ecd2a79
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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