Water → (1E,4E)-ethyl 2-(tert-butoxycarbonylamino)-8-(3-cyanophenyl)-3H-benzo[b]azepine-4-carboxylate

HRID 38013

Reaction equation

HRID 38013 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:25]=1)[N:7]=[C:8]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:9][C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:11]2.[C:26]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)#[N:27].[F-].[Cs+].O>C1COCC1.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>[C:21]([O:20][C:18]([NH:17][C:8]1[CH2:9][C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:11][C:5]2[CH:4]=[CH:3][C:2]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([C:26]#[N:27])[CH:33]=3)=[CH:25][C:6]=2[N:7]=1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 27343253-Cyanophenylboronic acidHCID 58228529Ethyl 8-bromo-2-((tert-butoxycarbonyl)amino)-3H-benzo[b]azepine-4-carboxylate

Product 1

HCID 86653481(1E,4E)-ethyl 2-(tert-butoxycarbonylamino)-8-(3-cyanophenyl)-3H-benzo[b]azepine-4-carboxylateYield 52%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1E,4E)-ethyl 8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylate (2.05 g, 5 mmol), 3-cyanophenylboronic acid (1.47 g, 10 mmol), CsF (2.28 g, 15 mmol), and Pd(PPh3)4 (0.345 g, 0.3 mmol) in anhydrous THF (100 mL) was refluxed for 12 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography to afford 1.12 g (52%) of (1E,4E)-ethyl 2-(tert-butoxycarbonylamino)-8-(3-cyanophenyl)-3H-benzo[b]azepine-4-carboxylate.

Workup

  1. temperaturewas refluxed for 12 h
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude material that
  7. customwas purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-036b2186255e45f59b78f09bfc018353
Source dataset
uspto-grants-2013_09
Patent number
US08524702B2

Linked notes

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