Cesium carbonate → Methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate

HRID 1894956ノート

反応式

HRID 1894956 の反応式
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Br[C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][C:48]([C:54]([O:56][CH3:57])=[O:55])=[CH:47]2.[C:58](=[O:65])([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])[NH2:59].C(=O)([O-])[O-].[Cs+].[Cs+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:61]([O:60][C:58]([NH:59][C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][C:48]([C:54]([O:56][CH3:57])=[O:55])=[CH:47]2)=[O:65])([CH3:64])([CH3:63])[CH3:62]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 53465709Methyl 6-bromoquinoline-3-carboxylate

生成物 1

HCID 67002181Methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate収率 76%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a round bottom flask under dry nitrogen were added palladium(II) acetate (100 mg, 0.6 mmol), Xantphos (600 mg, 1 mmol), methyl 6-bromoquinoline-3-carboxylate (1.5 g, 5.64 mmol), t-butyl carbamate (0.99 g, 8.4 mmol) and cesium carbonate (3.67 g, 11.3 mmol). Dry 1,4-dioxane (30 mL) was added by syringe and the mixture was stirred at 100° C. under dry nitrogen for 4 h. The reaction mixture was cooled to room temperature, diluted with water and extracted three times with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude mixture was purified by silica gel chromatography (hexanes to 1:1 hexanes/ethyl acetate gradient) to afford methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate (Int-2, 1.29 g, 76%). LC-MS: (FA) ES+ 303; 1H NMR (400 MHz, d6-DMSO) δ ppm 9.86 (s, 1H), 9.14 (d, J=2.1 Hz, 1H), 8.82 (d, J=1.9 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.00 (d, J=9.1 Hz, 1H), 7.87 (dd, J=9.1, 2.4 Hz, 1H), 3.93 (s, 3H), 1.51 (s, 9H).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted three times with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified by silica gel chromatography (hexanes to 1:1 hexanes/ethyl acetate gradient)

出典と根拠

ORDレコード
ord-9ef9a5547faf4556b681255236d59fbd
出典データセット
uspto-grants-2013_08
特許番号
US08513421B2

反応ノート

読み込み中…