Water → (R)-4-{4-{{2-[6-(2,2-dimethylpropionyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-4,5-dimethoxyphenyl}ethylcarbamoyl}phenyl}piperidine-1-carboxylic acid tert-butyl ester

HRID 1950223Notes

Reaction equation

HRID 1950223 reaction equation
C(N[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[C@@H:14]1[CH2:23][CH2:22][C:21]2[CH:20]=[C:19]([O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[CH:18]=[CH:17][C:16]=2[CH2:15]1)C.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([C:44]2[CH:49]=[CH:48][C:47]([C:50](Cl)=[O:51])=[CH:46][CH:45]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].[CH:53]([N:56](CC)C(C)C)(C)[CH3:54].O>O1CCOCC1>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([C:44]2[CH:49]=[CH:48][C:47]([C:50](=[O:51])[NH:56][CH2:53][CH2:54][C:4]3[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=3[C@@H:14]3[CH2:23][CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:24][C:25](=[O:30])[C:26]([CH3:28])([CH3:27])[CH3:29])[CH:20]=4)[CH2:15]3)=[CH:46][CH:45]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 57934541pivalic acid (R)-6-(2-ethylamino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl esterHCID 866052454-(4-Chlorocarbonylphenyl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66626255(R)-4-{4-{{2-[6-(2,2-dimethylpropionyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-4,5-dimethoxyphenyl}ethylcarbamoyl}phenyl}piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of pivalic acid (R)-6-(2-ethylamino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl ester (100 mg) and 4-(4-chlorocarbonylphenyl)piperidine-1-carboxylic acid tert-butyl ester (125 mg) in 1,4-dioxane (2 ml) was added N,N-diisopropylethylamine (0.45 ml), and the solution was stirred for 4 hours at 90° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide (R)-4-{4-{{2-[6-(2,2-dimethylpropionyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-4,5-dimethoxyphenyl}ethylcarbamoyl}phenyl}piperidine-1-carboxylic acid tert-butyl ester (189 mg). Synthesized from this compound (60 mg) according to an analogous synthetic method to Example 337 described below and purified by LC-MS, the title compound (29 mg) was obtained.

Workup

  1. stirringby stirring
  2. extractionthe solution was extracted with ethyl acetate
  3. washsequentially washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated in vacuo
  6. customThe residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system)

Sources & evidence

ORD record
ord-46fae855c5b34a938ab3c4544bc4897c
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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