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 2423750Notes

Reaction equation

HRID 2423750 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-5e0ce8e915d040e1a6444723596508fb
Source dataset
uspto-grants-2011_06
Patent number
US07960412B2

Reaction notes

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