Cesium carbonate → Methyl cis(+/-)-4-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)pyridine-2-carboxylate

HRID 43752

反応式

HRID 43752 の反応式
Cl.[CH3:2][O:3][C@H:4]1[C@@H:9]([NH:10][C:11](=[O:20])[O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8][CH2:7][NH:6][CH2:5]1.Cl[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH2:13]([O:12][C:11]([NH:10][C@H:9]1[CH2:8][CH2:7][N:6]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:23]=2)[CH2:5][C@H:4]1[O:3][CH3:2])=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 820890Methyl 4-ChloropicolinateHCID 86648698Benzyl cis(+/-)-[3-methoxypiperidin-4-yl]carbamate hydrochloride

生成物 1

HCID 86648699Methyl cis(+/-)-4-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)pyridine-2-carboxylate収率 32.3%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

実験手順

Benzyl cis(±)-[3-methoxypiperidin-4-yl]carbamate hydrochloride obtained in Example (160a) (192.83 mg, 0.64 mmol) and methyl 4-chloropyridine-2-carboxylate (100 mg, 0.58 mmol) were dissolved in dioxane (3 ml) and DMF (1 mL). Palladium acetate (26.17 mg, 0.12 mmol), BINAP (145.16 mg, 0.23 mmol) and cesium carbonate (569.68 mg, 1.75 mmol) were added, and the mixture was stirred using a microwave irradiation reactor at 160° C. for 40 minutes. Water was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1) to obtain 74.8 mg of the title compound as a yellow oily substance.

後処理

  1. customa microwave irradiation reactor at 160° C. for 40 minutes
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThereafter, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1)

出典と根拠

ORDレコード
ord-f635cac799ac48cfaad64c6aa0fa050d
出典データセット
uspto-grants-2013_09
特許番号
US08536197B2

関連ノート

読み込み中…