Sodium Hydroxide → {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

HRID 1950161Notes

Reaction equation

HRID 1950161 reaction equation
[F:1][CH2:2][C:3]([O-])=O.[Na+].C(Cl)(=O)C(Cl)=O.[OH-].[Na+].[Si:15]([O:22][C:23]1[CH:24]=[CH:25][C:26]([CH:47]2[CH2:56][CH2:55][C:54]3[C:49](=[CH:50][CH:51]=[C:52]([O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:60])[CH3:59])[CH:53]=3)[CH2:48]2)=[C:27]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][N:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)=[C:33]([F:46])[CH:32]=2)[CH:28]=1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>ClCCl.CN(C)C=O>[Si:15]([O:22][C:23]1[CH:24]=[CH:25][C:26]([CH:47]2[CH2:56][CH2:55][C:54]3[C:49](=[CH:50][CH:51]=[C:52]([O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:59])[CH3:60])[CH:53]=3)[CH2:48]2)=[C:27]([N:29]([CH2:3][CH2:2][F:1])[CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][N:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)=[C:33]([F:46])[CH:32]=2)[CH:28]=1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 16212360Sodium FluoroacetateHCID 57934032{5-(tert-Butyldimethylsilyloxy)-2-[6-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]phenyl}[3-fluoro-4-(2-piperidin-1-yl-ethoxy)benzyl]amine

Product 1

HCID 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]amineYield 62.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of sodium fluoroacetate (420 mg) in dichloromethane (20 ml) were added dropwise N,N-dimethylformamide (1 drop) and oxalyl chloride (0.48 ml) on an ice bath, the solution was stirred for 20 minutes at room temperature, an aqueous solution of 1N sodium hydroxide was added thereto, the solution was stirred for 1 minute at room temperature, then a solution of {5-(tert-butyldimethylsilyloxy)-2-[6-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]phenyl}[3-fluoro-4-(2-piperidin-1-yl-ethoxy)benzyl]amine (300 mg) in dichloromethane (5 ml) was added thereto followed by stirring at room temperature for 3 hours. The solution extracted with dichloromethane, then washed with brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. Synthesized from the resulting residue according to an analogous synthetic method to Example 337 described below, the title compound (200 mg) was obtained.

Workup

  1. stirringthe solution was stirred for 1 minute at room temperature
  2. stirringby stirring at room temperature for 3 hours
  3. extractionThe solution extracted with dichloromethane
  4. washwashed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated in vacuo
  7. customSynthesized from the resulting residue

Sources & evidence

ORD record
ord-4309ee52b7094ec99536d5c165d3a73f
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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