2-Chloromethyl 2-(trimethylsilyl)ethyl ether → HCID 86651953, compound

HRID 1615266Notes

Reaction equation

HRID 1615266 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([CH:11]=[O:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH3:13][Si:14]([CH2:17][CH2:18][O:19][CH2:20]Cl)([CH3:16])[CH3:15]>C(Cl)Cl.[OH-].[K+].CCCC[N+](CCCC)(CCCC)CCCC.[Br-]>[Br:1][C:2]1[CH:10]=[C:9]([CH:11]=[O:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH2:20][O:19][CH2:18][CH2:17][Si:14]([CH3:16])([CH3:15])[CH3:13]

Participants

6

Reactant 2

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 596355854-Bromo-1H-indazole-6-carboxaldehyde

Product 1

HCID 86651953HCID 86651953, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolventHCID 14797Potassium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-bromo-1H-indazole-6-carbaldehyde (225 mg, 1 mmol) in CH2Cl2 (10 mL) and aqueous KOH (2 mL, 50% wt) at 0° C. was added TBAB (3 mg, 0.01 mmol) and SEMCl (200 mg, 1.2 mmol). The mixture was stirred at 0° C. for 4 h, warmed to rt and extracted with ethyl acetate (100 mL). The organic phase was washed with water (2×10 mL) and brine (10 mL), dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (1:1 EtOAc/Hex) to give the title compound as a pale yellow solid (280 mg, 82%). 1H NMR (400 MHz, CD3OD) δ 10.02 (s, 1H), 8.21-8.19 (m, 2H), 7.80 (s, 1H), 5.78 (s, 2H), 3.70-3.65 (m, 2H), 0.95-0.92 (m, 2H), −0.05 (s, 9H).

Workup

  1. temperaturewarmed to rt
  2. extractionextracted with ethyl acetate (100 mL)
  3. washThe organic phase was washed with water (2×10 mL) and brine (10 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (1:1 EtOAc/Hex)

Sources & evidence

ORD record
ord-9eb12490dad24e6580fa33006e17dcd0
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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