Sodium hydride → (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(quinolin-7-yl-methoxy)-piperidine-1-carboxylic acid tert-butylester

HRID 650738Notes

Reaction equation

HRID 650738 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].Br.Br[CH2:37][C:38]1[CH:47]=[C:46]2[C:41]([CH:42]=[CH:43][CH:44]=[N:45]2)=[CH:40][CH:39]=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][CH2:37][C:38]2[CH:47]=[C:46]3[C:41]([CH:42]=[CH:43][CH:44]=[N:45]3)=[CH:40][CH:39]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11305954(3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl esterHCID 217130867-(Bromomethyl)quinoline--hydrogen bromide (1/1)

Product 1

HCID 57033058(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(quinolin-7-yl-methoxy)-piperidine-1-carboxylic acid tert-butylesterYield 85.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.40 g (7.20 mmol) of (3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butylester and 2.18 g (7.20 mmol) of 7-bromomethyl-quinoline hydrobromide (1:1) [J. Am. Chem. Soc. 77, 1054(1955)], were dissolved in 50 ml of absolute dimethylformamide under argon and then 0.83 g (19.0 mmol) of sodium hydride dispersion (55% in mineral oil) was added at room temperature in small portions. Subsequently, the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured onto ice-water, the product was extracted 3 times with ethyl acetate, the combined organic phases were washed twice with distilled water, then dried over magnesium sulphate, filtered and concentrated. The crude product (5.2 g, yellow oil) was chromatographed on silica gel with ethyl acetate/hexane 2:1 to yield 3.77 g (85.4% of theory) of (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(quinolin-7-yl-methoxy)-piperidine-1-carboxylic acid tert-butylester as a colourless oil; MS: 613 (M+H)+.

Workup

  1. additionThe reaction mixture was poured onto ice-water
  2. extractionthe product was extracted 3 times with ethyl acetate
  3. washthe combined organic phases were washed twice with distilled water
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product (5.2 g, yellow oil) was chromatographed on silica gel with ethyl acetate/hexane 2:1

Sources & evidence

ORD record
ord-036b68e44526406d8d05ad508e4df8a1
Source dataset
uspto-grants-2001_08
Patent number
US06274735B1

Reaction notes

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