Cesium carbonate → Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 237510

Reaktionsgleichung

Reaktionsgleichung von HRID 237510
Br[C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[O:12][C:13]1[CH:26]=[CH:25][C:16]2[C@H:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:18][O:19][C:15]=2[CH:14]=1.[CH3:27][C:28]1[CH:33]=[C:32]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39])[CH:31]=[C:30]([CH3:42])[C:29]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:42][C:30]1[CH:31]=[C:32]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:39])=[O:40])[CH:33]=[C:28]([CH3:27])[C:29]=1[C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[O:12][C:13]1[CH:26]=[CH:25][C:16]2[C@H:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:18][O:19][C:15]=2[CH:14]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 86697103{(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester2×HCID 866971722-(2,6-Dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Produkt 1

HCID 86697171Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetateAusbeute 20,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Methyl 2-((S)-6-((R)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate [intermediate 1, step 3] (32 mg), 2-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (42 mg), [1,1′-bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (6 mg), 1,1′-bis(diphenylphosphino)-ferrocene (4 mg) and caesium carbonate (50 mg) are suspended in toluene (2 mL) and degassed for 5 minutes with a flow of nitrogen. The mixture is heated under microwave irradiation for 90 minutes at 120° C. The mixture is diluted with ethyl acetate, washed with water, the organic phase dried and the solvent removed under vacuum. The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 100:0→50:50) to give the title compound (9 mg). LC (method 19): tR=1.38 min; Mass spectrum: m/z=583 [M+H]+.

Aufarbeitung

  1. customdegassed for 5 minutes with a flow of nitrogen
  2. additionThe mixture is diluted with ethyl acetate
  3. washwashed with water
  4. customthe organic phase dried
  5. customthe solvent removed under vacuum
  6. customThe residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 100:0→50:50)

Quellen und Nachweise

ORD-Eintrag
ord-77fc04c6f6774be492d87f6c4292db09
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642585B2

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