Sodium Carbonate → (rac)-2-(1-{[1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarbonyl]-amino}-indan-5-yl)-benzoic acid methyl ester

HRID 2046571Notes

Reaction equation

HRID 2046571 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][C:12]([C:14]1([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:16][CH2:15]1)=[O:13])[CH2:6][CH2:5]2.[CH3:24][O:25][C:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O)=[O:27].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.[Pd](Cl)Cl>[CH3:24][O:25][C:26](=[O:27])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][C:12]([C:14]1([NH:17][C:18](=[O:23])[C:19]([F:20])([F:21])[F:22])[CH2:15][CH2:16]1)=[O:13])[CH2:6][CH2:5]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27734962-(Methoxycarbonyl)benzeneboronic acidHCID 893915571-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid ((rac)-5-bromo-indan-1-yl)-amide

Product 1

HCID 60142024(rac)-2-(1-{[1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarbonyl]-amino}-indan-5-yl)-benzoic acid methyl esterYield 92.1%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid ((rac)-5-bromo-indan-1-yl)-amide (intermediate A-1 [B]) (0.20 g, 511 μmol) and 2-(methoxycarbonyl)phenylboronic acid (184 mg, 1.02 mmol) were dissolved in dioxane (9.0 ml); then, sodium carbonate (163 mg, 1.53 mmol), dissolved in water, was added while stirring. Subsequently, (1,1′-bis-diphenylphosphino)-ferrocene)palladium-(II)dichloride (1:1 complex with CH2Cl2) (18.7 mg, 25.6 μmol, eq: 0.05) was added and the reaction mixture was heated up to 50° C. for 5 hours. It was then poured into H2O (50 ml) and extracted with EtOAc (2×25 mL). The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give a crude product (0.296 g) which was purified by flash chromatography (silica gel, 20 g, 0% to 2% MeOH in CH2Cl2) to yield the title compound (0.21 g, 91%) as light brown oil. MS: 445.1 (M−H−).

Workup

  1. additionwas added
  2. extractionextracted with EtOAc (2×25 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a crude product (0.296 g) which
  7. customwas purified by flash chromatography (silica gel, 20 g, 0% to 2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-fe3e3209a24042e9b8df04b5bfeb9657
Source dataset
uspto-grants-2013_11
Patent number
US08592426B2

Reaction notes

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