Sodium hydride → tert-butyl (3RS,4RS,5SR)-4-(4-chloro-phenyl)-3-naphthalen-2-ylmethoxy-5-propyl-piperidine-1-carboxylate

HRID 1005075Notes

Reaction equation

HRID 1005075 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH:15]([CH2:16][CH2:17][CH3:18])[CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12][CH:11]2[OH:26])=[CH:6][CH:5]=1.Br[CH2:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=1>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH:15]([CH2:16][CH2:17][CH3:18])[CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12][CH:11]2[O:26][CH2:28][C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 703202-BromomethylnaphthaleneHCID 86604427tert-butyl (3RS,4RS,5SR)-4-(4-chloro-phenyl)-3-hydroxy-5-propyl-piperidine-1-carboxylate

Product 1

HCID 86604425tert-butyl (3RS,4RS,5SR)-4-(4-chloro-phenyl)-3-naphthalen-2-ylmethoxy-5-propyl-piperidine-1-carboxylateYield 77.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

37 mg (0.85 mmol) of sodium hydride (55% dispersion in refined oil) were added to a solution of 200 mg (0.56 mmol) of tert-butyl (3RS,4RS,5SR)-4-(4-chloro-phenyl)-3-hydroxy-5-propyl-piperidine-1-carboxylate and 188 mg (0.85 mmol) of 2-bromomethylnaphthalene in 10 ml of dimethylformamide and the reaction mixture was stirred at room temperature for 5 hours. For the working-up, the reaction mixture was evaporated in an oil pump vacuum, the residue was partitioned between water and ether and thereafter the separated aqueous phase was extracted five times with 50 ml of ether each time. The combined ether extracts were washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 96:4 mixture of toluene and ethyl acetate as the eluent. There were obtained 215 mg (77% of theory) of tert-butyl (3RS,4RS,5SR)-4-(4-chloro-phenyl)-3-naphthalen-2-ylmethoxy-5-propyl-piperidine-1-carboxylate as a colourless oil; MS: 494 (M+H)+.

Workup

  1. customthe reaction mixture was evaporated in an oil pump vacuum
  2. customthe residue was partitioned between water and ether
  3. extractionthe separated aqueous phase was extracted five times with 50 ml of ether each time
  4. washThe combined ether extracts were washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. customevaporated under reduced pressure
  7. customFor purification
  8. customthe crude product was chromatographed on silica gel using
  9. additiona 96:4 mixture of toluene and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-6fe6da80cf4f4cba9339a0bdf2da0c11
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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