Ammonia → Pivalic acid 6-{2-{ethyl[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yloxy)benzyl]amino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester

HRID 1950180Notes

Reaction equation

HRID 1950180 reaction equation
[CH2:1]([NH:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2].[CH3:29][N:30]1[CH:35]2[CH2:36][CH2:37][CH:31]1[CH2:32][CH:33]([O:38][C:39]1[CH:46]=[CH:45][C:42]([CH:43]=O)=[CH:41][CH:40]=1)[CH2:34]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].N>ClCCCl.O1CCCC1.C(O)(=O)C>[CH2:1]([N:3]([CH2:43][C:42]1[CH:41]=[CH:40][C:39]([O:38][CH:33]2[CH2:34][CH:35]3[N:30]([CH3:29])[CH:31]([CH2:37][CH2:36]3)[CH2:32]2)=[CH:46][CH:45]=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 5049666Sodium triacetoxyborohydrideHCID 579340574-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yloxy)benzaldehydeHCID 579340956-(2-(Ethylamino)-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl pivalate

Product 1

HCID 57933883Pivalic acid 6-{2-{ethyl[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yloxy)benzyl]amino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl esterYield 55.7%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of pivalic acid 6-(2-ethylamino-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl ester (65 mg) and 4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yloxy)benzaldehyde (65 mg) in 1,2-dichloroethane (2 ml) were sequentially added acetic acid (0.07 ml) and sodium triacetoxyborohydride (120 mg) under a nitrogen atmosphere, and the solution was stirred overnight at room temperature. Tetrahydrofuran and aqueous ammonia were sequentially 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 the title compound (58 mg).

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-70492d7fa1844eef8b045fa4edeb8e3a
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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