Hexane → HCID 23353532, compound

HRID 235141Notes

Reaction equation

HRID 235141 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[C:9]([N:12]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:8]=[CH:7]2.CCCCCC.C([Li])CCC.[CH3:38][N:39]1[CH2:44][CH2:43][C:42](=[O:45])[CH2:41][CH2:40]1>O1CCCC1>[CH2:20]([N:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[CH:4][CH:3]=[C:2]2[C:42]2([OH:45])[CH2:43][CH2:44][N:39]([CH3:38])[CH2:40][CH2:41]2)=[CH:7][CH:8]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 740491-Methyl-4-piperidoneHCID 23353480HCID 23353480, compoundHCID 178418339Butyllithium

Product 1

HCID 23353532HCID 23353532, compoundYield 138.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The following reaction was run in two side by side reactions and the crude products were combined for work up and purification. A mechanically stirred solution of 8-bromo-2-(dibenzylamino)-naphthalene (10.0 g, 24.9 mmol from Preparation 4) in tetrahydrofuran (200 mL) was cooled to -95° C. (hexane/liquid nitrogen) and butyllithium (10.39 mL, 24.9 mmol, 2.4 M) was added dropwise. The orange solution was stirred 7 min, then 1-methyl-4-piperidone (2.82 g, 24.9 mmol) was added dropwise over 10 minutes with a 10 mL tetrahydrofuran rinse. The orange color faded while stirring was continued 20 minutes at -100° C. The reaction was allowed to warm to room temperature and quenched with water. The solvent was removed and the residue was partitioned between methylene chloride and water (at this point the two reactions were combined). The phases were separated and the organic layer was washed with brine, dried, and concentrated onto silica gel. Flash chromatography (4×4 inches silica gel) proceeded as follows: methylene chloride (1 L) and 2% methanol/methylene chloride (1.6 L) unweighed white solid 7-dibenzylaminonaphthalene; 15% methanol / methylene chloride (1 L), 25% methanol/methylene chloride (1 L) and 30% methanol/methylene chloride/0.2% ammonium hydroxide (4 L) product contaminated with water. The combined eluents were concentrated and redissolved in methylene chloride. The solution was dried and concentrated to afford 15.09 g (69%) of 7-dibenzylamino-1-(4-hydroxy-1-methyl-4-piperidinyl)-naphthalene as a light tan foam. A sample recrystallized from ethyl acetate had mp 173°-174° C. Analysis calculated for C30H32N2O: C, 82.53; H, 7.39; N, 6.42. Found: C, 82.42; H, 7.44; N, 6.38.

Workup

  1. customThe following reaction
  2. custompurification
  3. additionwas added dropwise
  4. washrinse
  5. stirringwhile stirring
  6. waitwas continued 20 minutes at -100° C
  7. customquenched with water
  8. customThe solvent was removed
  9. customthe residue was partitioned between methylene chloride and water (at this point the two reactions
  10. customThe phases were separated
  11. washthe organic layer was washed with brine
  12. customdried
  13. concentrationconcentrated onto silica gel
  14. concentrationThe combined eluents were concentrated
  15. dissolutionredissolved in methylene chloride
  16. customThe solution was dried
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-895693e75fa04359a4b3a85a83d33950
Source dataset
uspto-grants-1997_01
Patent number
US05597826

Reaction notes

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