Potassium Carbonate → ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate

HRID 661906Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 661906
Br[C:2]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[NH2:16])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:8][C:9]=1[NH:10]2.[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:15]([C:12]1[CH:13]=[CH:14][C:2]([C:25]2[C:24]([F:23])=[CH:29][CH:28]=[CH:27][C:26]=2[F:30])=[C:3]2[C:11]=1[NH:10][C:9]1[CH2:8][CH:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:6][CH2:5][C:4]2=1)(=[O:17])[NH2:16]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 27343362,6-Difluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59375013ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate2×

Produkt 1

HCID 46834100ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylateAusbeute 45,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate (Intermediate 47-1, 20 mg, 0.055 mmol), 2,6-difluorophenylboronic acid (17.3 mg, 0.110 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.5 mg, 11.0 mmol), potassium carbonate (15.1 mg, 0.110 mmol) and tris(dibenzylideneacetone)dipalladium (5.0 mg, 0.005 mmol) in THF (2 mL) was purged with nitrogen for 2 min, then was heated in a sealed tube overnight. The mixture was filtered and concentrated, and the residue was purified by preparative HPLC. The appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The combined organic phases were washed with water, dried and concentrated to provide ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate as a light yellow solid (10 mg, 44%). 1H NMR (400 MHz, chloroform-d) δ 10.10 (1H, br. s.), 7.31-7.44 (2H, m), 6.95-7.06 (3H, m), 4.10-4.22 (2H, m), 2.96-3.12 (2H, m), 2.80 (1H, dddd, J=17.52, 5.99, 3.08, 2.86 Hz), 2.27-2.41 (1H, m), 2.15-2.27 (1H, m), 2.04-2.14 (1H, m), 1.69-1.85 (1H, m), 1.26 (3H, t, J=7.25 Hz). Mass spectrum m/z 399.1 (M+H)+.

Aufarbeitung

  1. customwas purged with nitrogen for 2 min
  2. temperaturewas heated in a sealed tube overnight
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated
  5. customthe residue was purified by preparative HPLC
  6. extractionextracted twice with DCM
  7. washThe combined organic phases were washed with water
  8. customdried
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-eed51b2f7f25476d98e6579317f9c2a1
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084620B2

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