Sodium hydride → HCID 131734678, compound

HRID 1772665Notes

Reaction equation

HRID 1772665 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([F:13])[F:12].[H-].[Na+].[CH3:16][Si:17]([CH2:20][CH2:21][O:22][CH2:23]Cl)([CH3:19])[CH3:18].[NH4+].[Cl-]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:23][O:22][CH2:21][CH2:20][Si:17]([CH3:19])([CH3:18])[CH3:16])[C:6](=[O:11])[C:5]2([F:13])[F:12]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 226077815-Bromo-3,3-difluoro-1,3-dihydro-indol-2-one

Product 1

HCID 131734678HCID 131734678, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-3,3-difluoroindolin-2-one (600 mg, 2.42 mmol) in DMF (5 mL), 60% NaH (69.6 mg, 2.90 mmol) was added. The resulting mixture was stirred at rt for 20 min and SEM-Cl (472 μL, 2.66 mmol) was added. The reaction mixture was stirred at rt overnight, poured into saturated NH4Cl (40 mL) and extracted with DCM (3×20 mL). The combined DCM layers were dried over Na2SO4, filtered, and concentrated. The residue obtained was purified by flash column chromatography on silica gel (0-100% EtOAc/hexanes) to obtain 5-bromo-3,3-difluoro-1-((2-(trimethylsilyl)ethoxy)methyl)indolin-2-one, which was subjected to borylation using the methods described in Example 32, Step B to obtain compound 37a. 1H-NMR (CDCl3, 400 MHz) δ (ppm): 8.33 (s, 1H), 8.04 (d, J=9.6 Hz, 1H), 7.57 (d, J=8.6 Hz, 1H), 5.46 (s, 2H), 3.75 (m, 2H), 1.27 (s, 12H), 0.95 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred at rt overnight
  2. extractionextracted with DCM (3×20 mL)
  3. dry with materialThe combined DCM layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue obtained
  7. customwas purified by flash column chromatography on silica gel (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c415a93b6a244ecc923c2ee90527a5c0
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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