Hydrochloric Acid → 1-Benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1411059ノート

反応式

HRID 1411059 の反応式
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9](Br)=[CH:8]2)=[O:4].[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.CCOC(C)=O.O>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:30]1[CH:31]=[CH:32][C:27]([C:26]([F:37])([F:36])[F:25])=[CH:28][CH:29]=1)=[CH:8]2)=[O:4]

参加物

10

反応物 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

生成物 1

HCID 682971661-Benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester収率 65.2%

試薬・触媒・溶媒 5

HCID 167845palladium(II) acetate触媒HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
105 °C

実験手順

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (220 mg, 0.57 mmol), 4-(trifluoromethyl)phenylboronic acid (161 mg, 0.85 mmol), K3PO4 (240 mg, 1.13 mmol), H2O (20 mg, 1.13 mmol), SPhos (12 mg, 0.028 mmol) and Pd(OAc)2 (12 mg, 0.017 mmol) in toluene (10 mL) was heated at 105° C. under nitrogen atmosphere for 20 h. After the mixture was cooled to r.t., water and EtOAc were added. 1 M HCl was added until pH was about 3, and the aqueous layer was extracted with additional EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH) to give 169 mg of the title compound as a yellow solid. MS: (+) m/z 455.34 (M+1).

後処理

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionthe aqueous layer was extracted with additional EtOAc
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH)

出典と根拠

ORDレコード
ord-2a5215969cd64bd59c9dbd8483dbe515
出典データセット
uspto-grants-2014_12
特許番号
US08921389B2

反応ノート

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