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

HRID 237440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 237440
[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:48]([CH3:49])=[CH:47][C:39]([O:40][CH2:41][CH:42]2[CH2:46][CH2:45][O:44][CH2:43]2)=[CH:38][C:37]=1[CH3:50].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1>[CH3:50][C:37]1[CH:38]=[C:39]([O:40][CH2:41][CH:42]2[CH2:46][CH2:45][O:44][CH2:43]2)[CH:47]=[C:48]([CH3:49])[C:36]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[C:10]2[C:6]=1[CH2:7][CH2:8][C@H:9]2[O:11][C:12]1[CH:25]=[CH:24][C:15]2[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=2[CH:13]=1

Komponenten

5

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 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 esterHCID 866971073-((4-Bromo-3,5-dimethylphenoxy)methyl)tetrahydrofuran

Produkt 1

HCID 86697108Methyl 2-((3S)-6-((1R)-4-(2,6-dimethyl-4-((tetrahydrofuran-3-yl)methoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

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 (170 mg) and 3-((4-bromo-3,5-dimethylphenoxy)methyl)tetrahydrofuran (170 mg) and K3PO4 (290 mg) are suspended in tetrahydrofuran (10 mL). The mixture is purged for 5 minutes with argon. [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium (27 mg) is added, the vial is sealed and the mixture is stirred at 100° C. for 12 hours. After cooling to room temperature the mixture is diluted with diethylether and washed with saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→50:50) to give the title compound. Yield: 47 mg; LC (method 1): tR=1.48 min; Mass spectrum (ESI+): m/z=569 [M+Na]+.

Aufarbeitung

  1. customThe mixture is purged for 5 minutes with argon
  2. addition[1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium (27 mg) is added
  3. customthe vial is sealed
  4. temperatureAfter cooling to room temperature the mixture
  5. additionis diluted with diethylether
  6. washwashed with saturated aqueous NH4Cl solution
  7. dry with materialThe organic phase is dried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→50:50)

Quellen und Nachweise

ORD-Eintrag
ord-ba440bd6a29f4069a3b9dd738dbfe184
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642585B2

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