Tetrahydrofuran → HCID 89649287, compound

HRID 2207616Notes

Reaction equation

HRID 2207616 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([C:10]2[CH2:14][CH2:13][C@:12]3([CH2:18][CH2:17][NH:16][C:15]3=[O:19])[N:11]=2)[CH:5]=1.Cl[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26].[CH2:29]1COCC1>>[Br:3][C:4]1[CH:9]=[C:8]([CH3:29])[N:7]=[C:6]([C:10]2[CH2:14][CH2:13][C@:12]3([CH2:18][CH2:17][N:16]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]3=[O:19])[N:11]=2)[CH:5]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 89648829HCID 89648829, compound

Product 1

HCID 89649287HCID 89649287, compound

Procedure

Method B Sodium hydride (60% dispersion in oil, 26.03 mg, 0.6500 mmol) was added in two portions to a stirred solution of (5R)-2-(4-bromo-2-pyridyl)-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 19) (174.mg, 0.5900 mmol) in dry THF (8 mL) at ambient temperature under nitrogen. After stirring for 45 mins, 2-(chloromethoxy)-ethyl-trimethyl-silane (0.12 mL, 0.6500 mmol) was added dropwise over 2 minutes. The reaction mixture was stirred over the weekend. The reaction mixture was quenched by the addition of saturated ammonium chloride solution (20 ml) and the product extracted with dichloromethane twice. The combined organic extracts were passed through a hydrophobic frit and the solvent evaporated at reduced pressure. The product was purified by silica gel chromatography eluting with 0-100% ethyl acetate in iso-hexane to give a colourless solid (199 mg) (5R)-2-(4-bromo-6-methyl-2-pyridyl)-7-(2-trimethylsilylethoxymethyl)-1,7-diazaspiro[4.4]non-1-en-6-one (D42R) (199 mg);

Workup

  1. stirringThe reaction mixture was stirred over the weekend
  2. customThe reaction mixture was quenched by the addition of saturated ammonium chloride solution (20 ml)
  3. extractionthe product extracted with dichloromethane twice
  4. customthe solvent evaporated at reduced pressure
  5. customThe product was purified by silica gel chromatography
  6. washeluting with 0-100% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-8c06f34049974717ababe9b92e002f86
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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