Water → (1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol

HRID 1912615Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1912615
[F:1][C:2]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:20])=[C:12]([C:15](OCC)=[O:16])[C:13]([I:14])=[C:8]2[CH:7]=[CH:6]1.CC(C[AlH]CC(C)C)C.O.[OH-].[Na+].O>ClCCl>[F:1][C:2]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:20])=[C:12]([CH2:15][OH:16])[C:13]([I:14])=[C:8]2[CH:7]=[CH:6]1

Komponenten

6

Edukt 4

HCID 962Water2×HCID 14487Diisobutylaluminum hydrideHCID 23719242Sodium hydroxide--water (1/1/1)HCID 71209259ethyl 1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

Produkt 1

HCID 71209443(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanolAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of ethyl 1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (10 g, 21.92 mmol) in dichloromethane (DCM) (160 mL) at −55° C. under nitrogen atmosphere was added dropwise DIBAL-H (129 mL, 129 mmol) (1M/toluene) in ˜20 min and then the mixture was allowed to warm to 0° C. in 1 h and stirred at 0° C. for 1.5 h. The mixture was cooled to −20° C. and water (5.2 mL) was added dropwise followed by 15% NaOH/water (5.2 mL) and water (12.9 ml) and stirring at ambient temperature continued for 30 min. The mixture was filtered through celite washing with dichloromethane. The filtrate was concentrated and dried in vacuo to provide (1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol (8.76 g, 19.67 mmol, 90% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.70 (t, J=6.05 Hz, 1 H), 2.82 (s, 3 H), 4.99 (d, J=6.05 Hz, 2 H), 5.51 (s, 2 H), 6.32 (d, J=3.52 Hz, 1 H), 6.81-6.89 (m, 1 H), 6.90-7.00 (m, 1 H), 7.07 (dd, J=9.67, 1.86 Hz, 1 H), 7.19 (d, J=3.52 Hz, 1 H); LCMS (m/z) ES+=415 (M+1).

Aufarbeitung

  1. temperatureThe mixture was cooled to −20° C.
  2. stirringstirring at ambient temperature
  3. waitcontinued for 30 min
  4. filtrationThe mixture was filtered
  5. washthrough celite washing with dichloromethane
  6. concentrationThe filtrate was concentrated
  7. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-5f3a64e2475e4003b31b986c2113bd37
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609653B2

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