Ethyl Acetate → HCID 178502287, compound

HRID 1504309Notes

Reaction equation

HRID 1504309 reaction equation
[CH3:1][O:2][C:3](=[O:32])[NH:4][C@H:5]([C:9]([N:11]1[C@H:19]([C:20]2[NH:21][CH:22]=[C:23]([C:25]3[CH:30]=[CH:29][C:28](Br)=[CH:27][CH:26]=3)[N:24]=2)[CH2:18][C:13]2([O:17][CH2:16][CH2:15][O:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:33]([O:37][C:38](=[O:60])[NH:39][C:40]1[CH:45]=[CH:44][C:43](B2OC(C)(C)C(C)(C)O2)=[C:42]([O:55][C:56]([F:59])([F:58])[F:57])[CH:41]=1)([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:33]([O:37][C:38](=[O:60])[NH:39][C:40]1[CH:45]=[CH:44][C:43]([C:28]2[CH:29]=[CH:30][C:25]([C:23]3[N:24]=[C:20]([C@@H:19]4[CH2:18][C:13]5([O:17][CH2:16][CH2:15][O:14]5)[CH2:12][N:11]4[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:32])[CH:6]([CH3:8])[CH3:7])[NH:21][CH:22]=3)=[CH:26][CH:27]=2)=[C:42]([O:55][C:56]([F:58])([F:59])[F:57])[CH:41]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 67495502HCID 67495502, compoundHCID 178502285HCID 178502285, compound

Product 1

HCID 178502287HCID 178502287, compoundYield 133.9%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ((S)-1-{(S)-8-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (350 mg, 0.69 mmol) in dioxane (8 mL) and water (4 mL) was added [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethoxy-phenyl]-carbamic acid tert-butyl ester (334 mg, 0.83 mmol), sodium carbonate (148 mg, 1.4 mmol), and tetrakis(triphenylphosphine)-palladium(0) (81 mg, 0.07 mmol). The reaction mixture was stirred at reflux for 3 h under nitrogen. Ethyl acetate (50 mL) was added and the solution was washed with brine, dried over sodium sulfate, filtered, and concentrated to give the title intermediate as a yellow solid (650 mg). (m/z): [M+H]+ calcd for C34H49N5O8 704.28. found 704.3.

Workup

  1. temperatureat reflux for 3 h under nitrogen
  2. washthe solution was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f5962518cd2e433e91cce220f95fe0c0
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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