Ammonium Chloride → 1-(Tert-butyl) 3-methyl 4-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)-5,6-dihydropyridine-1,3(2h)-dicarboxylate

HRID 658230ノート

反応式

HRID 658230 の反応式
[Si:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[CH3:24][O:25][C:26]([C:28]1[CH2:29][N:30]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:31][CH2:32][C:33]=1OS(C(F)(F)F)(=O)=O)=[O:27].[NH4+].[Cl-]>C1COCC1.[Cl-].[Cl-].[Zn+2].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.CCOC(C)=O>[CH3:24][O:25][C:26]([C:28]1[CH2:29][N:30]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:31][CH2:32][C:33]=1[C:15]1[CH:16]=[CH:17][C:12]([O:11][CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:13][CH:14]=1)=[O:27]

参加物

9

反応物 4

HCID 25517Ammonium ChlorideHCID 150978074-[2-(Tert-butyldimethylsilanyloxy)ethoxy]bromobenzeneHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 178418339Butyllithium

生成物 1

HCID 684912491-(Tert-butyl) 3-methyl 4-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)-5,6-dihydropyridine-1,3(2h)-dicarboxylate収率 82.4%

試薬・触媒・溶媒 4

HCID 3007855Zincchloride触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

To a sol. of 4-[2-(tert-butyldimethylsilanyloxy)ethoxy]bromobenzene (WO 03/093267, 7.95 g, 24 mmol) in THF (200 mL) at −78° C. was added BuLi (1.6M in hexane, 17.12 mL, 27.4 mmol). The sol. was stirred at −78° C. for 30 min, then ZnCl2 (1M in THF, 30 mL, 30 mmol) was added. The resulting sol. was allowed to warm to rt, and 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957, 7.79 g, 20 mmol) in THF (20 mL) and Pd(PPh3)4 (0.69 g, 0.60 mmol) were added. The reaction mixture was heated to 50° C. for 1 h, and stirred 16 h at rt. The mixture was cooled to 0° C., and aq. sat. NH4Cl was added. EtOAc was added, and the org. phase was washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 2:8→1:0) yielded the title compound (8.1 g, 82%). LC-MS: tR=1.23 min, ES+: 506.47.

後処理

  1. temperatureto warm to rt
  2. temperatureThe reaction mixture was heated to 50° C. for 1 h
  3. stirringstirred 16 h at rt
  4. temperatureThe mixture was cooled to 0° C.
  5. washphase was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customPurification of the residue by FC (EtOAc/heptane 2:8→1:0)

出典と根拠

ORDレコード
ord-0f98cd4c79cc43459a5a141e034a4541
出典データセット
uspto-grants-2011_12
特許番号
US08076359B2

反応ノート

読み込み中…