Triethylamine → N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}-N'-(3,5-dimethylbenzoyl)sulfamide

HRID 23749

Reaktionsgleichung

Reaktionsgleichung von HRID 23749
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([OH:7])=O.ClS(N=C=O)(=O)=O.[CH2:19]([N:26]([CH2:31][CH:32]1[CH2:37][CH2:36][CH:35]([CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[CH2:34][CH2:33]1)[S:27]([NH2:30])(=[O:29])=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C>ClCCl>[CH2:19]([N:26]([CH2:31][CH:32]1[CH2:37][CH2:36][CH:35]([CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:41])[CH3:42])[CH2:34][CH2:33]1)[S:27]([NH:30][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([CH3:11])[CH:10]=[C:2]([CH3:1])[CH:3]=1)(=[O:28])=[O:29])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 103563,5-Dimethylbenzoic acidHCID 70918Chlorosulfonyl isocyanateHCID 22574471N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}sulfamide

Produkt 1

HCID 20757669N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}-N'-(3,5-dimethylbenzoyl)sulfamideAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

3,5-Dimethylbenzoic acid (1.50 g, 10.0 mmole, 1.0 eq) was suspended in 5 mL dichloromethane and heated to reflux, after which a solution of chlorosulfonyl isocyanate (0.87 mL, 10.0 mmole, 1.0 eq) in 2 mL dichloromethane was added. Reaction mixture became clear, and remained so after 40 minutes of reflux. Cooled to room temperature, added hexanes and began to evaporate when solid precipitated out. Recovered filtered solid. 23 mg, 92 μmole, 1.0 eq of this material was added to a mixture of intermediate (2) (34 mg, 92 μmole, 1.0 eq) and triethylamine (39 μL, 277 μmole, 3.0 eq) in dichloromethane (0.5 mL). Reaction was complete at 2 hours, at which point it was purified directly by silica gel chromatography to give the title compound in 86% yield. 1H NMR (500 MHz, DMSO-d6): δ 11.84 (s, 1H), 7.49 (s, 2H), 7.31 (m, 6H), 4.52 (s, 2H), 3.28 (d, 2H), 3.09 (d, 2H), 2.30 (s, 6H), 1.58 (m, 4H), 1.31 (m, 1H), 1.22 (m, 1H), 0.82 (s, 9H), 0.66 (m, 4H), 0.04 (s, 6H). N-benzyl-N′-(3,5-dimethylbenzoyl)-N-{[4-(hydroxymethyl)cyclohexyl]methyl}sulfamide (38): Intermediate (37) was treated as (3) was treated in the synthesis of (4) to give the title alcohol in quantitative yield. 1H NMR (500 MHz, DMSO-d6): δ 11.85 (s, 1H), 7.50 (s, 2H), 7.31 (m, 6H), 4.52 (s, 2H), 4.27 (t, 1H), 3.10 (m, 4H), 2.32 (s, 6H), 1.59 (m, 4H), 1.31 (m, 1H), 1.22 (m, 1H), 0.66 (m, 4H). {4-[(benzyl{[(3,5-dimethylbenzoyl)amino]sulfonyl}amino)methyl]cyclohexyl}methyl phenylcarbamate (39): Alcohol (38) (34.6 mg, 78 mmole, 1.0 eq) in 0.5 mL dichloromethane was treated with triethylamine (38 mL, 272 mmole, 3.5 eq) and phenyl isocyanate (17 mL, 156 mmole, 2.0 eq) to give the title compound after preparative TLC. 1H NMR (500 MHz, DMSO-d6): δ 11.85 (s, 1H), 9.52 (s, 1H), 7.50 (s, 2H), 7.41 (d, 2H), 7.36 (d, 2H), 7.30 (t, 2H), 7.24 (t, 3H), 7.19 (s, 1H), 6.95 (t, 1H), 4.48 (s, 2H), 3.800 (d, 2H), 3.07 (d, 2H), 2.32 (s, 6H), 1.64 (m, 4H), 1.47 (m, 1H), 1.34 (m, 1H), 0.73 (m, 4H).

Aufarbeitung

  1. temperatureheated
  2. temperatureto reflux
  3. customReaction mixture
  4. temperatureof reflux
  5. customto evaporate when solid
  6. customprecipitated out
  7. customRecovered
  8. filtrationfiltered solid
  9. customReaction
  10. waitwas complete at 2 hours, at which point it
  11. customwas purified directly by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-54e8d92af288423ab066c8b7a907c207
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06852738B2

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