Sodium hydride → HCID 66817371, compound

HRID 1755051Notes

Reaction equation

HRID 1755051 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]([N:38]([CH3:42])[C:39](Cl)=[O:40])[CH:7]=[C:8]([CH3:37])[C:9]=1/[CH:10]=[CH:11]/[S:12]([N:15]1[CH2:36][CH2:35][C:18]2([N:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:33])([F:32])[F:31])[CH:24]=3)[NH:20][C:19]2=[O:34])[CH2:17][CH2:16]1)(=[O:14])=[O:13].[C:43]([Si:47]([CH3:53])([CH3:52])[O:48][CH2:49][CH2:50][OH:51])([CH3:46])([CH3:45])[CH3:44]>O1CCCC1>[C:43]([Si:47]([CH3:53])([CH3:52])[O:48][CH2:49][CH2:50][O:51][C:39](=[O:40])[N:38]([C:6]1[CH:5]=[C:4]([CH3:3])[C:9](/[CH:10]=[CH:11]/[S:12]([N:15]2[CH2:36][CH2:35][C:18]3([N:22]=[C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:31])([F:33])[F:32])[CH:24]=4)[NH:20][C:19]3=[O:34])[CH2:17][CH2:16]2)(=[O:13])=[O:14])=[C:8]([CH3:37])[CH:7]=1)[CH3:42])([CH3:46])([CH3:45])[CH3:44]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111376652-(tert-Butyl(dimethyl)silyl)oxyethanolHCID 86672781N-(3,5-dimethyl-4-{(E)-2-[4-oxo-2-(3-trifluoromethoxy-phenyl)-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl]-vinyl}-phenyl)-N-methyl-chloroformamide

Product 1

HCID 66817371HCID 66817371, compoundYield 78.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% oil suspension, 5.6 mg, 0.14 mmol) was added to a solution of N-(3,5-dimethyl-4-{(E)-2-[4-oxo-2-(3-trifluoromethoxy-phenyl)-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl]-vinyl}-phenyl)-N-methyl-chloroformamide (30 mg, 50.1 μmol) in tetrahydrofuran (1.0 ml) at 0° C., and the mixture was stirred for 15 minutes. 2-(tert-Butyl-dimethyl-silanyloxy)-ethanol (30 μL, 0.14 mmol) was then added and the mixture was stirred at 40° C. for two hours. The mixture was cooled, and then quenched with water and extracted with ethyl acetate. The organic layer was sequentially washed with water and saturated brine, and then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (dichloromethane-ethyl acetate) to give (3,5-dimethyl-4-{(E)-2-[4-oxo-2-(3-trifluoromethoxy-phenyl)-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl]-vinyl}-phenyl)-methyl-carbamic acid 2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester (29 mg, 78%).

Workup

  1. stirringthe mixture was stirred at 40° C. for two hours
  2. temperatureThe mixture was cooled
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was sequentially washed with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (dichloromethane-ethyl acetate)

Sources & evidence

ORD record
ord-98020c66b02e46288d714a427ca3929e
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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