Sodium hydride → HCID 57135446, compound

HRID 650736Notes

Reaction equation

HRID 650736 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([OH:34])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:36][C:37]1[CH:46]=[CH:45][C:44]2[C:39](=[CH:40][C:41]([O:47][CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])=[CH:42][CH:43]=2)[CH:38]=1.[H-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:36][C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[CH:40][C:41]([O:47][CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:53])([CH3:55])[CH3:54])=[CH:42][CH:43]=3)[CH:38]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111630832-Chloromethyl-7-(2-trimethylsilanyl-ethoxymethoxy)-naphthaleneHCID 11305954(3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57135446HCID 57135446, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

25.4 g (53.86 mmol) of (3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butylester and 17.78 g (55.06 mmol) of 2-chloromethyl-7-(2-trimethylsilanyl-ethoxymethoxy)-naphthalene (WO 97/09311) were dissolved in 180 ml of dimethylformamide under argon and then 2.49 g (57.09 mmol) of sodium hydride dispersion (55% in mineral oil) was added. Subsequently, the mixture was stirred at room temperature for 5 hours. The reaction mixture was poured onto ice-water, the product was extracted 3 times with methylene chloride, the organic phases were washed twice with distilled water, then dried over magnesium sulphate, filtered and concentrated in a water-jet vacuum. The resulting crude product was chromatographed on silica gel with methylene chloride and methanol to give 36.43 g (89.2% of theory) of (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[7-(2-trimethylsilanyl-ethoxymethoxy)-naphthalen-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butylester as a yellowish oil; MS: 759 (M+H)+.

Workup

  1. additionThe reaction mixture was poured onto ice-water
  2. extractionthe product was extracted 3 times with methylene chloride
  3. washthe organic phases were washed twice with distilled water
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in a water-jet vacuum
  7. customThe resulting crude product was chromatographed on silica gel with methylene chloride and methanol

Sources & evidence

ORD record
ord-5a019fa60e4343ecab9c91bb6fbd1113
Source dataset
uspto-grants-2001_08
Patent number
US06274735B1

Reaction notes

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