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

HRID 658230노트

반응식

HRID 658230 반응식
[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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 3007855Zincchloride촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-0f98cd4c79cc43459a5a141e034a4541
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08076359B2

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