8-Methyl-8-azabicyclo(3.2.1)octan-3-ol → HCID 58023090, compound

HRID 1950319Notes

Reaction equation

HRID 1950319 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH:8]2[CH2:9][CH:10]([OH:12])[CH2:11][CH:5]1[CH2:6][CH2:7]2.C(NC1C=C(OC)C=CC=1C1CCC2C(=CC=C(OC)C=2)C1)C.FC1C=C(C=CC=1F)C(Cl)=O.[CH2:47]([N:49]([C:60]1[CH:65]=[C:64]([O:66][CH3:67])[CH:63]=[CH:62][C:61]=1[CH:68]1[CH2:77][CH2:76][C:75]2[C:70](=[CH:71][CH:72]=[C:73]([O:78][CH3:79])[CH:74]=2)[CH2:69]1)[C:50](=[O:59])[C:51]1[CH:56]=[CH:55][C:54](F)=[C:53]([F:58])[CH:52]=1)[CH3:48].C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:47]([N:49]([C:60]1[CH:65]=[C:64]([O:66][CH3:67])[CH:63]=[CH:62][C:61]=1[CH:68]1[CH2:77][CH2:76][C:75]2[C:70](=[CH:71][CH:72]=[C:73]([O:78][CH3:79])[CH:74]=2)[CH2:69]1)[C:50](=[O:59])[C:51]1[CH:56]=[CH:55][C:54]([O:12][CH:10]2[CH2:11][CH:5]3[N:4]([CH3:3])[CH:8]([CH2:7][CH2:6]3)[CH2:9]2)=[C:53]([F:58])[CH:52]=1)[CH3:48]

Participants

8

Reactant 6

HCID 84248-Methyl-8-azabicyclo(3.2.1)octan-3-olHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 27245193,4-Difluorobenzoyl chlorideHCID 23087318Ethyl[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]amineHCID 66627253N-ethyl-3,4-difluoro-N-[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]benzamide

Product 1

HCID 58023090HCID 58023090, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 60% sodium hydride (187 mg) in N,N-dimethylformamide (2 ml) was added tropine (599 mg) on an ice bath. The solution was stirred for 30 minutes while warming to room temperature. Synthesized from ethyl[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]amine and 3,4-difluorobenzoyl chloride according to an analogous synthetic method to Preparation Example 87, a solution of N-ethyl-3,4-difluoro-N-[5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]benzamide (383 mg) in N,N-dimethylformamide (5 ml) was added the above solution followed by stirring overnight at 80° C. The reaction mixture was let to cool, then a saturated aqueous solution of sodium bicarbonate was added thereto, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous potassium carbonate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (chloroform-methanol system) to provide the title compound (143 mg).

Workup

  1. stirringby stirring overnight at 80° C
  2. temperatureto cool
  3. extractionthe solution was extracted with ethyl acetate
  4. washsequentially washed with water and brine
  5. dry with materialdried over anhydrous potassium carbonate
  6. customthe solvent was evaporated in vacuo
  7. customThe residue was purified by NH silica gel column chromatography (chloroform-methanol system)

Sources & evidence

ORD record
ord-649d152c43ce4382afd6de4c98691e20
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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