Sodium Hydroxide → HCID 16005059, compound

HRID 44459Notes

Reaction equation

HRID 44459 reaction equation
CN(C)S([N:6]1[CH:10]=[CH:9][N:8]=[CH:7]1)(=O)=O.C([Li])CCC.Br[C:18]1[CH:23]=[CH:22][C:21]([C:24]23[CH2:31][N:28]([CH2:29][CH2:30]2)[CH2:27][CH2:26][CH2:25]3)=[CH:20][N:19]=1.[OH-].[Na+]>O1CCCC1.CCCCCC.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)(Cl)Cl>[NH:8]1[CH:9]=[CH:10][N:6]=[C:7]1[C:18]1[CH:23]=[CH:22][C:21]([C:24]23[CH2:31][N:28]([CH2:29][CH2:30]2)[CH2:27][CH2:26][CH2:25]3)=[CH:20][N:19]=1

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 395751N,N-Dimethyl-1H-imidazole-1-sulfonamideHCID 862593785-(2-Bromopyrid-5-yl)-1-azabicyclo[3.2.1]octaneHCID 178418339Butyllithium

Product 1

HCID 16005059HCID 16005059, compound

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalyst2×HCID 178418397HCID 178418397, compoundCatalystHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

1 g (5.7 mmol) of 1-(dimethylaminosulfonyl)imidazole dissolved in 9 ml of tetrahydrofuran is introduced into a 25 ml three-necked flask. The reaction medium is cooled to −78° C. and 4 ml of a 1.6M solution of n-butyllithium in hexane is added dropwise over 20 minutes. 0.73 g (5.4 mmol) of zinc chloride dissolved in 4 ml of tetrahydrofuran is then added. The mixture is stirred while allowing the temperature to return to 20° C., and 1.5 g (11.1 mmol) of zinc chloride, 0.1 g (0.09 mmol) of tetrakis(triphenylphosphine)palladium and 0.56 g (2.1 mmol) of (−)-5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]octane (prepared according to the method described in step 1.2 of Example 1), dissolved in 5 ml of tetrahydrofuran, are then successively added. The mixture is then refluxed for 24 hours and then cooled to room temperature. 30 ml of aqueous 30% sodium hydroxide solution and 50 ml of chloroform are added. The aqueous phase is extracted with chloroform and the combined organic phases are then washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica gel, eluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions and is used in the following step without further purification.

Workup

  1. additionis introduced into a 25 ml three-necked flask
  2. additionis then added
  3. customto return to 20° C.
  4. additionare then successively added
  5. temperatureThe mixture is then refluxed for 24 hours
  6. temperaturecooled to room temperature
  7. extractionThe aqueous phase is extracted with chloroform
  8. washthe combined organic phases are then washed with saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue is purified by chromatography on a column of silica gel
  13. washeluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions
  14. customis used in the following step without further purification

Sources & evidence

ORD record
ord-07e4670ecda44b67912d345f5548593e
Source dataset
uspto-grants-2013_09
Patent number
US08541440B2

Reaction notes

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