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

HRID 1433976Notes

Reaction equation

HRID 1433976 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

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-bbb1f2e096354926af264662d3e6870b
Source dataset
uspto-grants-2009_11
Patent number
US07612114B2

Reaction notes

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