Toluene → HCID 178502470, compound

HRID 1504323Notes

Reaction equation

HRID 1504323 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7](Br)=[C:6]([O:11][C:12]([F:15])([F:14])[F:13])[CH:5]=1.[CH3:17][O:18][C:19](=[O:54])[NH:20][C@H:21]([C:25]([N:27]1[CH2:31][C@@H:30]([S:32][CH3:33])[CH2:29][C@H:28]1[C:34]1[NH:35][CH:36]=[C:37]([C:39]2[CH:44]=[CH:43][C:42](B3OC(C)(C)C(C)(C)O3)=[CH:41][CH:40]=2)[N:38]=1)=[O:26])[CH:22]([CH3:24])[CH3:23].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>O>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:42]2[CH:43]=[CH:44][C:39]([C:37]3[N:38]=[C:34]([C@@H:28]4[CH2:29][C@H:30]([S:32][CH3:33])[CH2:31][N:27]4[C:25](=[O:26])[C@@H:21]([NH:20][C:19]([O:18][CH3:17])=[O:54])[CH:22]([CH3:24])[CH3:23])[NH:35][CH:36]=3)=[CH:40][CH:41]=2)=[C:6]([O:11][C:12]([F:15])([F:14])[F:13])[CH:5]=1)=[O:16]

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 59300634Methyl 4-bromo-3-(trifluoromethoxy)benzoateHCID 178502468HCID 178502468, compound

Product 1

HCID 178502470HCID 178502470, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-bromo-3-trifluoromethoxy-benzoic acid methyl ester (184 mg, 0.62 mmol), [(S)-2-methyl-1-((2S,4S)-4-methylsulfanyl-2-{4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (300 mg, 0.55 mmol) and potassium carbonate (344 mg, 2.49 mmol) at RT was added toluene (1.35 mL) followed by water (0.69 mL). The reaction mixture was purged with nitrogen, Pd(dppf)Cl2CH2Cl2 (27.4 mg, 0.034 mmol) was added under an atmosphere of nitrogen. The reaction vial was capped and heated at 100° C. overnight, cooled to RT and partitioned between EtOAc (10 mL) and water (2 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to give a brownish oil which was purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/Hexanes). Desired fractions were combined and concentrated to give the title intermediate as an orange oil. (m/z): [M+H]+ calcd for C30H33F3N4O6S 635.21. found 635.

Workup

  1. additionwas added under an atmosphere of nitrogen
  2. customThe reaction vial was capped
  3. temperaturecooled to RT
  4. custompartitioned between EtOAc (10 mL) and water (2 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brownish oil which
  9. customwas purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/Hexanes)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-380bb532c78b47679f0542391d39ea15
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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