Dimethylformamide → HCID 178497461, Verbindung

HRID 724361Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 724361
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[Li]C1C=CC=CC=1.[Li]C(CC)C.CN([CH:38]=[O:39])C>C1COCC1>[CH3:22][O:21][C:13]1[CH:12]=[C:11]([C:7]2[CH:6]=[C:5]3[C:10]([C:2]([CH:38]=[O:39])=[N:3][NH:4]3)=[CH:9][CH:8]=2)[CH:16]=[CH:15][C:14]=1[O:17][CH2:18][O:19][CH3:20]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 178418400CID 53628100HCID 178497462HCID 178497462, VerbindungHCID 178506676HCID 178506676, Verbindung

Produkt 1

HCID 178497461HCID 178497461, VerbindungAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

In a 100-mL round-bottom flask, 3-iodo-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole (921 mg, 2.245 mmol, 1.00 equiv) was dissolved in THF (36 mL) and cooled to −78° C. (allow 8 min at this scale). A solution of PhLi (2.5 mL, 1.8 M, 4.49 mmol, 2.00 equiv) was added and the mixture was allowed to stir for 30 min. A solution of s-BuLi (3.63 mL, 4.71 mmol, 2.1 equiv) was added and the reaction mixture was allowed to stir for 1 h at −78° C. Neat DMF (1.4 mL, 18 mmol, 8.0 equiv) was added. The cold bath was removed and the reaction was allowed to slowly warm to 0° C. in the air. As the ice melted saturated sodium bicarbonate (20 mL) was added. The product was extracted into ethyl acetate (200 mL) from saturated sodium bicarbonate (75 mL more), dried over sodium sulfate, decanted and concentrated under reduced pressure. Purification by silica gel chromatography (450 mL silica, 4:6 ethyl acetate/hexane) gave 6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole-3-carbaldehyde (498 mg, 71%)): Rf sm 0.30, p 0.14 (ethyl acetate-hexane 4:6); 1H NMR (CDCl3) δ 10.85 (bs, 1H), 10.25 (s, 1H), 8.37 (d, 1H, J=8.4 Hz), 7.67 (s, 1H), 7.60 (d, 1H, J=8.4 Hz), 6.26 (d, 1H, J=8.7 Hz), 7.19 (m, 2H), 5.30 (s, 2H), 3.99 (s, 3H), 3.55 (s, 3H).

Aufarbeitung

  1. stirringto stir for 1 h at −78° C
  2. customThe cold bath was removed
  3. temperatureto slowly warm to 0° C. in the air
  4. additionAs the ice melted saturated sodium bicarbonate (20 mL) was added
  5. extractionThe product was extracted into ethyl acetate (200 mL) from saturated sodium bicarbonate (75 mL more),
  6. dry with materialdried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated under reduced pressure
  9. customPurification by silica gel chromatography (450 mL silica, 4:6 ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-2eee67f69bb34845b7ec9776c3f474bc
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07141587B2

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