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

HRID 132604

반응식

HRID 132604 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c5516325d1e747e4b2dcb8908a65f597
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388021B2

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