Potassium Phosphate, Tribasic → Methyl 2-((3S)-6-((1R)-4-(3-cyano-2-methylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 237511Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 237511
[F:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]2[C:10]=1[C@H:9]([O:11][C:12]1[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=1)[CH2:8][CH2:7]2.Br[C:36]1[C:37]([CH3:44])=[C:38]([CH:41]=[CH:42][CH:43]=1)[C:39]#[N:40].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:39]([C:38]1[C:37]([CH3:44])=[C:36]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[C:10]3[C:6]=2[CH2:7][CH2:8][C@H:9]3[O:11][C:12]2[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=2)[CH:43]=[CH:42][CH:41]=1)#[N:40]

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 234335373-Bromo-2-methylbenzonitrileHCID 86697106{(S)-6-[(R)-7-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Produkt 1

HCID 86697173Methyl 2-((3S)-6-((1R)-4-(3-cyano-2-methylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a microwave vial, methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate (200 mg), 3-bromo-2-methylbenzonitrile (169 mg), K3PO4 (274 mg), Palladium-(II)-acetate (10 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (18 mg) are suspended in toluene (10 mL) and water (2 mL) and purged for 10 minutes with argon. The vial is sealed and the mixture is stirred at 100° C. for 4 hours. After cooling to ambient temperature the mixture is partitioned between ethyl acetate and water. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10) to give the title compound. Yield: 124 mg; LC (method 20): tR=8.09 min; Mass spectrum (ESI+): m/z=558 [M+−H]+.

Aufarbeitung

  1. customwater (2 mL) and purged for 10 minutes with argon
  2. customThe vial is sealed
  3. temperatureAfter cooling to ambient temperature the mixture
  4. customis partitioned between ethyl acetate and water
  5. dry with materialThe organic phase is dried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10)

Quellen und Nachweise

ORD-Eintrag
ord-f9f692b66305428d811f97a27d54bfea
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642585B2

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