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

HRID 1374172ノート

反応式

HRID 1374172 の反応式
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]

参加物

9

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒3 回HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-168116942ba6493eac5b8159a1226610
出典データセット
uspto-grants-2007_01
特許番号
US07163951B2

反応ノート

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