Potassium Carbonate → 4-[7-Chloro-1-oxo-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-1H-isoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 2427517ノート

反応式

HRID 2427517 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH:34]=[C:35]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([Cl:11])[CH:10]=2)[C:7](=[O:12])[N:6]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:23])([F:22])[F:24])=[CH:16][CH:15]=2)[CH2:5]3)[CH2:36][CH2:37]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 117044755-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one

生成物 1

HCID 579494284-[7-Chloro-1-oxo-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-1H-isoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester収率 23.3%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

5-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one (190.0 mg, 0.452 mmol), 4-(4,4,5,5-Tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert butyl ester (140.0 mg, 0.452 mmol), potassium carbonate (187.0 mg, 1.36 mmol), and PdCl2(dppf) (37.0 mg, 0.045 mmol) were suspended in anhydrous dimethyl formamide (2 mL) and the mixture was heated to 110° C. After nineteen hours, the heating was stopped and the cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The product was purified by column chromatography (30% EtOAc/Hexanes) to provide the title compound as a colourless solid (55.0 mg, 23%.) 1H NMR (300 MHz, CDCl3): δ 7.38 (m, 3H), 7.26 (s, 1H), 7.18 (d, 2H), 6.18 (broad s, 1H), 4.79 (s, 2H), 4.25 (s, 2H), 4.11 (broad s, 2H), 3.65 (t, 2H), 2.5 (broad s, 2H), 1.49 (s, 9H).

後処理

  1. waitAfter nineteen hours
  2. customthe cooled reaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by column chromatography (30% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-5419c4aefe4a455f877e84e3cacd5ae1
出典データセット
uspto-grants-2011_06
特許番号
US07968570B2

反応ノート

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