Sodium hydride → tert-butyl N-methyl-N-(4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yloxy]cyclohexyl)carbamate

HRID 525106

Reaktionsgleichung

Reaktionsgleichung von HRID 525106
[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([N:8]([CH3:16])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:20]1[N:21]=[CH:22][N:23]=[C:24]2[C:31]=1[C:30]1[CH2:29][CH2:28][CH2:27][C:26]=1[S:25]2>C1COCC1>[CH3:16][N:8]([CH:5]1[CH2:6][CH2:7][CH:2]([O:1][C:20]2[N:21]=[CH:22][N:23]=[C:24]3[C:31]=2[C:30]2[CH2:29][CH2:28][CH2:27][C:26]=2[S:25]3)[CH2:3][CH2:4]1)[C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 78981712-Chloro-7-thia-9,11-diazatricyclo(6.4.0.0,2,6)dodeca-1(12),2(6),8,10-tetraeneHCID 219251474-(N-Boc-N-methylamino)cyclohexanol

Produkt 1

HCID 68110120tert-butyl N-methyl-N-(4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yloxy]cyclohexyl)carbamateAusbeute 74,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl N-(4-hydroxycyclohexyl)-N-methylcarbamate (447 mg, 1.95 mmol, 1.30 equiv) in anhydrous THF (30 mL), then sodium hydride (300 mg, 7.50 mmol, 5.00 equiv, 60% dispersion in mineral oil) was added and stirring for 20 min at room temperature under nitrogen. Then 12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (316 mg, 1.50 mmol, 1.00 equiv) was added and stirred for 6 h at ambient temperature. The reaction mixture was quenched with NH4Cl (sat.) at 0° C., diluted with brine, extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified by a silica gel column with EA/PE (1:10-1:4) to provide tert-butyl N-methyl-N-(4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yloxy]cyclohexyl)carbamate (450 mg, 74%) as a white solid. MS: (ES, m/z): 404 [M+H]+.

Aufarbeitung

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringstirred for 6 h at ambient temperature
  4. customThe reaction mixture was quenched with NH4Cl (sat.) at 0° C.
  5. additiondiluted with brine
  6. extractionextracted with EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationAfter filtration and concentration
  10. customthe residue was purified by a silica gel column with EA/PE (1:10-1:4)

Quellen und Nachweise

ORD-Eintrag
ord-0210bef3cc0344a8871b125f04cf92b2
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340554B2

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