Sodium Carbonate → 4'-Amino-3'-fluoro[1,1'-biphenyl]-2-carbaldehyde

HRID 132604

反応式

HRID 132604 の反応式
[CH:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O)=[O:2].Br[C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[C:15]([F:20])[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[C:15]([F:20])[CH:14]=1)=[O:2]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 1230504-Bromo-2-fluoroanilineHCID 2921892-Formylphenylboronic acid

生成物 1

HCID 222887634'-Amino-3'-fluoro[1,1'-biphenyl]-2-carbaldehyde

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒

実験手順

4-(2′-N,N-Dimethylaminomethylphenyl)-2-fluoroaniline: To a solution of 2-formylphenylboronic acid (5 g, 33 mmol) in THF (80 mL) was added 4-bromo-2-fluoroaniline (4.2 g, 22 mmol) and sodium carbonate (2 M, 80 mL) and then was bubbled with nitrogen for 10 min. After Pd(PPh3)4 (1.54 g, 1.33 mmol) was added, the resulting mixture was refluxed under nitrogen for 4 h. The THF layer was separated and filtered through a pad of silica gel. The pad was washed with THF to give an 80 mL solution of 4(2′-formylphenyl)-2-fluoroaniline in THF. To the filtrate (15 mL from total 80 mL) was added Me2NH.HCl (0.68 g, 8.3 mmol) and the resulting mixture was refluxed for 2 h. The mixture was cooled to rt and MeOH (5 mL) was added followed by NaBH4 (0.32 g, 8.3 mmoL). After being stirred at 50° C. for 1 hour, the mixture was cooled to rt and quenched with 1 N HCl to pH 1. The aqueous layer was separated, neutralized with 50% NaOH to pH 12, and extracted with EtOAc. The EtOAc layer was dried over MgSO4, concentrated, and purified by SiO2 chromatography eluted with EtOAc to give 54a (0.89 g, 88% yield); [M+H]+=245.2; 1H NMR (CDCl3) δ 7.49 (dd, J=8.8 Hz, J=1.8 Hz, 1H), 7.31-7.21 (m, 3H), 7.14 (dd, J=12.1 Hz, J=1.8 Hz, 1H), 6.97 (dd, J=8.1 Hz, J=1.5 Hz, 1H), 6.80 (t, J=8.8 Hz, 1H), 3.76 (bs, 2H), 3.34 (s, 2H), 2.17 (s, 6H); 19F NMR (CDCl3) δ-136.19. This material was converted to the bis-HCl salt by dissolving a sample in a minimum volume of methanol and adding 2.2 equivalents of 1.0 M HCl in diethyl ether followed by removal of the solvent under reduced pressure.

後処理

  1. customwas bubbled with nitrogen for 10 min
  2. temperaturethe resulting mixture was refluxed under nitrogen for 4 h
  3. customThe THF layer was separated
  4. filtrationfiltered through a pad of silica gel
  5. washThe pad was washed with THF

出典と根拠

ORDレコード
ord-c5516325d1e747e4b2dcb8908a65f597
出典データセット
uspto-grants-2008_06
特許番号
US07388021B2

関連ノート

読み込み中…