Acetic Acid → HCID 44336319, compound

HRID 1281579Notes

Reaction equation

HRID 1281579 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:3]=1[CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22](OC)OC)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7].[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:43][CH2:44][C@@H:45]([C:47]1[CH:48]=[CH:49][C:50]([OH:58])=[C:51]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:52]=1)[OH:46].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[F:1][C:2]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:3]=1[CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][NH:43][CH2:44][C@H:45]([OH:46])[C:47]3[CH:48]=[CH:49][C:50]([OH:58])=[C:51]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:52]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7]

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18174046HCID 18174046, compound

Product 1

HCID 44336319HCID 44336319, compoundYield 46.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

N-(2,5-Difluorobenzyl)-4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinecarboxamide (0.30 g, 0.69 mmol) was added to a pre-prepared mixture of sodium iodide (0.16 g, 1.03 mmol) and trichloro(methyl)silane (0.132 mL, 1.05 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 10 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.062 mL, 1.02 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.17 g, 0.69 mmol) followed by sodium cyanoborohydride (0.047 g, 0.764 mmol). The reaction was stirred at room temperature for 24 hours. The reaction was taken to dryness in vacuo, adsorbed onto silica and purified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide) to yield the title compound (0.2 g, 0.32 mmol).

Workup

  1. washthe reaction washed with 10% sodium thiosulfate solution, water and brine
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent partially removed in vacuo
  5. stirringThe reaction was stirred at room temperature for 24 hours
  6. custompurified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide)

Sources & evidence

ORD record
ord-775d534d92424f7d89d6cbf063359cc1
Source dataset
uspto-grants-2002_09
Patent number
US06451814B1

Reaction notes

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