Acetic Acid → 1-[[4-[[4-[2-[[(2R)-2-Hydroxy-2-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]ethyl]amino]ethyl]phenyl]amino]-1-piperidinyl]carbonyl]-3-piperidine Carboxylic Acid, Ethyl Ester

HRID 1281581Notes

Reaction equation

HRID 1281581 reaction equation
CO[CH:3](OC)[CH2:4][C:5]1[CH:30]=[CH:29][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:19]3)=[O:17])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:44][CH2:45][C@@H:46]([C:48]1[CH:49]=[CH:50][C:51]([OH:59])=[C:52]([NH:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH:53]=1)[OH:47].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[OH:47][C@H:46]([C:48]1[CH:49]=[CH:50][C:51]([OH:59])=[C:52]([NH:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH:53]=1)[CH2:45][NH:44][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([NH:9][CH:10]2[CH2:11][CH2:12][N:13]([C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:19]3)=[O:17])[CH2:14][CH2:15]2)=[CH:29][CH:30]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173893Ethyl 1-([4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl}carbonyl)-3-piperidinecarboxylate

Product 1

HCID 865845851-[[4-[[4-[2-[[(2R)-2-Hydroxy-2-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]ethyl]amino]ethyl]phenyl]amino]-1-piperidinyl]carbonyl]-3-piperidine Carboxylic Acid, Ethyl EsterYield 4.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Ethyl 1-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl}carbonyl)-3-piperidinecarboxylate (1.0 g, 2.23 mmol) was added to a pre-prepared mixture of sodium iodide (0.893 g, 5.96 mmol) and trichloro(methyl)silane (0.561 mL, 4.77 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 (0.156 mL, 2.6 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide (0.587 g, 2.38 mmol) followed by sodium cyanoborohydride (0.164 g, 2.38 mmol). The reaction was stirred at ambient 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 (0.07 g, 0.11 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 ambient 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-3f30ce174d934e4dbaa412cbd9ea4c46
Source dataset
uspto-grants-2002_09
Patent number
US06451814B1

Reaction notes

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