Sodium Carbonate → methyl 2-(6-{(1R)-1-[(tert-butylsulfinyl)amino]-ethyl}-5-fluoropyridin-3-yl)-4,6-dichlorobenzoate

HRID 1374172Notes

Reaction equation

HRID 1374172 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:17])[C:5]([C@H:8]([NH:10][S:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH3:9])=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].ClC1C=C(C=CC=1)C(OO)=O.[Cl:52][C:53]1[CH:62]=[C:61]([Cl:63])[CH:60]=[C:59](OS(C(F)(F)F)(=O)=O)[C:54]=1[C:55]([O:57][CH3:58])=[O:56].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:13]([S:11]([NH:10][C@@H:8]([C:5]1[N:6]=[CH:7][C:2]([C:59]2[CH:60]=[C:61]([Cl:63])[CH:62]=[C:53]([Cl:52])[C:54]=2[C:55]([O:57][CH3:58])=[O:56])=[CH:3][C:4]=1[F:17])[CH3:9])=[O:12])([CH3:16])([CH3:15])[CH3:14]

Participants

9

Reactant 6

HCID 10340Sodium CarbonateHCID 70297m-Chloroperbenzoic acidHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diborane2×HCID 21075880Methyl 2,4-dichloro-6-{[(trifluoromethyl)sulfonyl]oxy}benzoateHCID 68520381N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide

Product 1

HCID 68515751methyl 2-(6-{(1R)-1-[(tert-butylsulfinyl)amino]-ethyl}-5-fluoropyridin-3-yl)-4,6-dichlorobenzoate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide (0.500 g, 1.55 mmol), bis(pinacolato)diboron (0.412 g, 1.62 mmol), potassium acetate (0.456 g, 4.64 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.030 g, 0.041 mmol) in 5 mL DMF was heated to 90° C. under N2 for 4 hours. Additional bis(pinacolato)diboron (0.295 g, 1.16 mmol) and 3-chloroperoxybenzoic acid (861 mg, 4.99 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.030 g, 0.041 mmol) were added to drive the reaction to completion. The reaction mixture was cooled to room temperature, and methyl 2,4-dichloro-6-{[(trifluoromethyl)sulfonyl]oxy}benzoate (0.546 g, 1.55 mmol), sodium carbonate (2M, 2.32 mL, 4.64 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]palladium (II) dichloride (0.003 g, 0.041 mmol) were added. The reaction mixture was heated to 90° C. 1.5 hours, then cooled to room temperature and partitioned between ethyl acetate and water. The organic extract was washed with water and brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 0–30% ethyl acetate in hexanes to provide methyl 2-(6-{(1R)-1-[(tert-butylsulfinyl)amino]-ethyl}-5-fluoropyridin-3-yl)-4,6-dichlorobenzoate that gave proton NMR spectra consistent with theory.

Workup

  1. customthe reaction to completion
  2. temperatureThe reaction mixture was cooled to room temperature
  3. temperatureThe reaction mixture was heated to 90° C
  4. temperature1.5 hours, then cooled to room temperature
  5. custompartitioned between ethyl acetate and water
  6. extractionThe organic extract
  7. washwas washed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. washeluted with 0–30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-168116942ba6493eac5b8159a1226610
Source dataset
uspto-grants-2007_01
Patent number
US07163951B2

Reaction notes

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