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Dichloromethane → ethyl ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603413
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 603413
Br[C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[C@H:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:14]3)=[C:4]([O:28][CH3:29])[CH:3]=1.[S:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.C(Cl)Cl.C([O-])(O)=O.[Na+]>COCCOC.O.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]>[CH3:29][O:28][C:4]1[CH:3]=[C:2]([C:32]2[CH:33]=[CH:34][S:30][CH:31]=2)[CH:27]=[CH:26][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[C@H:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:14]2
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 581760Thiophene-3-boronic acidHCID 59300414ethyl {(1S)-5-[3-(4-bromo-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate

Produkt 1

HCID 59300464ethyl ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateAusbeute 59,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Ethyl {(1S)-5-[3-(4-bromo-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate (140 mg, 0.3 mmol) (Example 97), 3-thiopheneboronic acid (81.2 mg, 0.63 mmol), PdCl2(dppf).CH2Cl2 (90.5 mg, 0.07 mmol), and NaHCO3 (76.1 mg, 0.91 mmol) were suspended in DME (10 mL) and water (1 mL). The reaction mixture was degassed under vacuum for 3 min, and then purged with argon, after which the reaction mixture was agitated by orbital shaker at 80° C. for 24 h, and then at rt for 24 h. The reaction mixture was filtered through a pad of silica gel, and the filtrate was concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (EtOAc/hexanes (v/v)=1:9 to 1:1 gradient) to give 83 mg (59%) of the title compound as a yellow oil. 1H NMR (400 MHz, acetone-d6): δ 7.62-7.71 (m, 1H), 7.52-7.46 (m, 2H), 7.29 (d, 1H), 7.23-7.19 (m, 1H), 7.11-7.09 (m, 1H), 7.02-6.99 (m, 1H), 6.83-6.82 (m, 1H), 6.76-6.73 (m, 1H), 4.22-4.09 (m, 6H), 3.87 (s, 3H), 3.44 (m, 1H), 2.87-2.66 (m, 3H), 2.40-2.18 (m, 4H), 1.74-1.70 (m, 1H), 1.25 (t, 3H).

Aufarbeitung

  1. customThe reaction mixture was degassed under vacuum for 3 min
  2. custompurged with argon
  3. waitat rt for 24 h
  4. filtrationThe reaction mixture was filtered through a pad of silica gel
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe crude material was purified by silica gel flash chromatography (EtOAc/hexanes (v/v)=1:9 to 1:1 gradient)

Quellen und Nachweise

ORD-Eintrag
ord-290d003658de4c0997932fa2559615c9
Quelldatensatz
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07906653B2

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