Water → HCID 59657562, compound

HRID 1865934Notes

Reaction equation

HRID 1865934 reaction equation
C([Li])CCC.Br[C:7]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][C:8]=1[C:9]([OH:11])=[O:10].[CH3:17][N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C:19]1=O.O>C1COCC1.CCCCCC.CCOCC>[Br:16][C:13]1[CH:14]=[CH:15][C:7]2[C:21]3([O:11][C:9](=[O:10])[C:8]=2[CH:12]=1)[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]3

Participants

8

Reactant 4

HCID 962WaterHCID 118912,5-Dibromobenzoic acidHCID 13603N-Methyl-2-piperidoneHCID 178418339Butyllithium

Product 1

HCID 59657562HCID 59657562, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Butyllithium (97.2 ml of 1.47 M solution in hexane, 143 mmol) was added dropwise to a solution of 2,5-Dibromo-benzoic acid (20 g, 72 mmol) in dry THF (300 ml) at −78° C. over a period of 3.5 h under a nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 2 h. A solution of N-methyl piperidone (11.31 g, 99 mmol) in hexane (40 mL) was added dropwise during 30 min to the reaction mixture at −78° C. The reaction mixture was allowed to come to room temperature and stirring was continued for overnight. The reaction mixture was added to a mixture of water (500 ml) and ether (300 mL). The aqueous layer was extracted with ether (5×150 mL) and acidified with concentrated HCl (to pH 2-3) and extracted with ether (2×150 ml). The acidic solution was boiled for 1 h and then cooled to 0-5° C. and made alkaline (to pH 9-10) with aqueous NaOH. The cold solution was rapidly extracted with chloroform (5×300 mL). The combined chloroform extracts were washed with water (150 ml), dried over sodium sulfate and evaporated under reduced pressure. The residue was purified was purified by silica gel (100-200) column chromatography eluting with methanol in dichloromethane (0.5% to 2.5%) to afford the desired product (4.2 g, 20%).

Workup

  1. customto come to room temperature
  2. stirringstirring
  3. waitwas continued for overnight
  4. extractionThe aqueous layer was extracted with ether (5×150 mL)
  5. extractionextracted with ether (2×150 ml)
  6. waitThe acidic solution was boiled for 1 h
  7. temperaturecooled to 0-5° C.
  8. extractionThe cold solution was rapidly extracted with chloroform (5×300 mL)
  9. washThe combined chloroform extracts were washed with water (150 ml)
  10. dry with materialdried over sodium sulfate
  11. customevaporated under reduced pressure
  12. customThe residue was purified
  13. customwas purified by silica gel (100-200) column chromatography
  14. washeluting with methanol in dichloromethane (0.5% to 2.5%)

Sources & evidence

ORD record
ord-bd1e770ccf7f4a009657eacc4d84ca09
Source dataset
uspto-grants-2009_12
Patent number
US07629353B2

Reaction notes

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