Ammonia → 6-{2-{(2-Fluoroethyl)[3-fluoro-4-(2-piperidin-1-ylethoxy)benzyl]amino}-4-hydroxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol

HRID 2423732Notes

Reaction equation

HRID 2423732 reaction equation
[Si]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH:36]2[CH2:45][CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[C:41]([O:46][Si](C(C)(C)C)(C)C)[CH:42]=3)[CH2:37]2)=[C:13]([N:15]([CH2:33][CH2:34][F:35])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[C:19]([F:32])[CH:18]=2)[CH:14]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl.CO.N>O1CCCC1>[F:35][CH2:34][CH2:33][N:15]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]2[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)=[C:19]([F:32])[CH:18]=1)[C:13]1[CH:14]=[C:9]([OH:8])[CH:10]=[CH:11][C:12]=1[CH:36]1[CH2:45][CH2:44][C:43]2[CH:42]=[C:41]([OH:46])[CH:40]=[CH:39][C:38]=2[CH2:37]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 2724141Tetrabutylammonium FluorideHCID 21893726Hydrochloride methanolHCID 57933781{5-(tert-Butyldimethylsilyloxy)-2-[6-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]phenyl}(2-fluoroethyl)[3-fluoro-4-(2-piperidin-1-ylethoxy)benzyl]amine

Product 1

HCID 579340976-{2-{(2-Fluoroethyl)[3-fluoro-4-(2-piperidin-1-ylethoxy)benzyl]amino}-4-hydroxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-olYield 99.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of {5-(tert-butyldimethylsilyloxy)-2-[6-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]phenyl}(2-fluoroethyl)[3-fluoro-4-(2-piperidin-1-ylethoxy)benzyl]amine (200 mg) in tetrahydrofuran (10 ml) were sequentially added tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran) (1 ml) and hydrochloric acid-methanol solution (1 ml) on an ice bath, and the solution was stirred for 8 hours at 50° C. The reaction solution was alkalinized by adding aqueous ammonia, the solution was extracted with ethyl acetate, then washed with 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-methanol system) to provide the title compound (140 mg).

Workup

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

Sources & evidence

ORD record
ord-d64c95d729264fccb4fef247d9c75f69
Source dataset
uspto-grants-2011_06
Patent number
US07960412B2

Reaction notes

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