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

HRID 661906ノート

反応式

HRID 661906 の反応式
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]

参加物

7

反応物 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 回

生成物 1

HCID 46834100ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate収率 45.6%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-eed51b2f7f25476d98e6579317f9c2a1
出典データセット
uspto-grants-2011_12
特許番号
US08084620B2

反応ノート

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