Sodium hydride → tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate

HRID 1004986Notes

Reaction equation

HRID 1004986 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH:9]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:17][C:18]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:12][CH:11]=2)[CH2:8][CH2:7][N:6]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:5]1.Br[CH2:45][C:46]1[CH:55]=[CH:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=1>CN(C)C=O>[CH:47]1[C:48]2[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:54]=[CH:55][C:46]=1[CH2:45][O:3][CH:4]1[CH:9]([C:10]2[CH:11]=[CH:12][C:13]([CH2:16][O:17][C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[CH:14][CH:15]=2)[CH2:8][CH2:7][N:6]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 703202-BromomethylnaphthaleneHCID 54169897tert-butyl (3RS,4RS)-3-hydroxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate

Product 1

HCID 54015520tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

290 mg (6.05 mmol) of sodium hydride (50% dispersion in refined oil) were added to a solution of 2.08 g (3.78 mmol) of tert-butyl (3RS,4RS)-3-hydroxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate and 1.0 g (4.54 mmol) of 2-bromomethyinaphthalene in 30 ml of dimethylformamide and the reaction mixture was stirred at room temperature for 2 hours. For the working-up, the reaction mixture was evaporated in an oil pump vacuum, the residue was partitioned between 100 ml of saturated ammonium chloride solution and 100 ml of ethyl acetate and thereafter the separated aqueous phase was extracted twice with 50 ml of ethyl acetate each time. The combined ethyl acetate extracts were dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 4:1 mixture of methylene chloride and hexane as the eluent. There were obtained 2.27 g (87% of theory) of tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate as a colourless solid; MS: 707 (M+NH4)+.

Workup

  1. customthe reaction mixture was evaporated in an oil pump vacuum
  2. customthe residue was partitioned between 100 ml of saturated ammonium chloride solution and 100 ml of ethyl acetate
  3. extractionthe separated aqueous phase was extracted twice with 50 ml of ethyl acetate each time
  4. dry with materialThe combined ethyl acetate extracts were dried over sodium sulphate
  5. customevaporated under reduced pressure
  6. customFor purification
  7. customthe crude product was chromatographed on silica gel using
  8. additiona 4:1 mixture of methylene chloride and hexane as the eluent

Sources & evidence

ORD record
ord-18afc5f87c2a4d6baac738ae1ed54768
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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