Sodium Hydroxide → 2-[(4-Benzyloxy-1-piperidinyl)methyl]-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine

HRID 565689Notes

Reaction equation

HRID 565689 reaction equation
Cl.[CH2:2]([O:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+].C(OC1CCNCC1)C1C=CC=CC=1.Br[CH2:33][C:34]1([CH3:47])[CH2:38][C:37]2[C:39]([CH3:46])=[C:40]([NH2:45])[C:41]([CH3:44])=[C:42]([CH3:43])[C:36]=2[O:35]1>C(OCC)(=O)C.C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+].C(N(CC)CC)C>[CH2:2]([O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:33][C:34]2([CH3:47])[CH2:38][C:37]3[C:39]([CH3:46])=[C:40]([NH2:45])[C:41]([CH3:44])=[C:42]([CH3:43])[C:36]=3[O:35]2)[CH2:12][CH2:11]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 31574604-(Benzyloxy)piperidineHCID 108505902-Bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamineHCID 128070004-(Benzyloxy)piperidine hydrochloride

Product 1

HCID 221110692-[(4-Benzyloxy-1-piperidinyl)methyl]-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamineYield 72%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
180 °C

Procedure

In ethyl acetate was suspended 2.0 g of 4-benzyloxypiperidine hydrochloride and the suspension was neutralized with aqueous 1N-auqeous sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. To a solution prepared by dissolving the resulting 4-benzyloxypiperidine in 0.5 mL of toluene were added 1.1 g of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine and 2.8 mL of triethylamine, and in an autoclave, the mixture was stirred under nitrogen gas at 180° C. for 15 hours. This reaction mixture was diluted with saturated aqueous NaHCO3 and extracted with 3 portions of ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, and filtered and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane/ethyl acetate=1:1) and recrystallized from ethyl acetate/hexane to provide 1.1 g of the title compound. Yield 67%.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe pooled organic layer was washed with water and saturated aqueous NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customTo a solution prepared
  8. extractionextracted with 3 portions of ethyl acetate
  9. washThe pooled organic layer was washed with water and saturated aqueous NaCl
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-558a614df4b24cec91e6fce11bd56a62
Source dataset
uspto-grants-2001_01
Patent number
US06172085B2

Reaction notes

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