Acetic Acid → HCID 69985672, compound

HRID 1281623Notes

Reaction equation

HRID 1281623 reaction equation
CO[CH:3](OC)[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][CH:20]=[C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:22]=3)[CH2:14][CH2:13]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:42][CH2:43][C@@H:44]([C:46]1[CH:47]=[CH:48][C:49]([OH:57])=[C:50]([NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[CH:51]=1)[OH:45].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[OH:57][C:49]1[CH:48]=[CH:47][C:46]([C@@H:44]([OH:45])[CH2:43][NH:42][CH2:3][CH2:4][C:5]2[CH:6]=[CH:7][C:8]([NH:11][CH:12]3[CH2:17][CH2:16][N:15]([C:18]4[S:19][CH:20]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[N:22]=4)[CH2:14][CH2:13]3)=[CH:9][CH:10]=2)=[CH:51][C:50]=1[NH:52][S:53]([CH3:56])(=[O:55])=[O:54]

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173889HCID 18173889, compound

Product 1

HCID 69985672HCID 69985672, compoundYield 9.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

N-[4-(2,2-Dimethoxyethyl)phenyl]-1-(4-phenyl-1,3-thiazol-2-yl)-4-piperidinamine (0.415 g, 30 0.98 mmol) was added to a pre-prepared mixture of sodium iodide (0.367 g, 2.45 mmol) and trichloro(methyl)silane (0.229 mL, 1.95 mmol) in anhydrous acetonitrile (70 mL). 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 with anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.088 mL, 1.47 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.241 g, 0.98 mmol) followed by sodium cyanoborohydride (0.067 g, 0.97 mmol). The reaction was stirred at ambient temperature overnight. 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 (0.092 mmol, 0.151 mmol).

Workup

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

Sources & evidence

ORD record
ord-8dc65024c49c4ceda8449d6d773c4d9d
Source dataset
uspto-grants-2002_09
Patent number
US06451814B1

Reaction notes

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