Sodium hydride → HCID 57079772, compound

HRID 1531521Notes

Reaction equation

HRID 1531521 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]S(C)(=O)=O)=[CH:16][CH:15]=2)[C@@H:10]([O:29][CH2:30][C:31]2[CH:40]=[C:39]3[C:34]([CH:35]=[CH:36][CH:37]=[N:38]3)=[CH:33][CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:41]1([CH2:44]O)[CH2:43][CH2:42]1.[H-].[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1>[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][CH2:44][CH:41]3[CH2:43][CH2:42]3)=[CH:16][CH:15]=2)[C@@H:10]([O:29][CH2:30][C:31]2[CH:40]=[C:39]3[C:34]([CH:35]=[CH:36][CH:37]=[N:38]3)=[CH:33][CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 516892Sodium BicarbonateHCID 57025369HCID 57025369, compound

Product 1

HCID 57079772HCID 57079772, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To an ice-cooled solution of 3.50 g (6.13 mmol) of the (3R,4R)-4-[4-(3-methanesulfonyloxy-propoxy)-phenyl]-3-(quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester and 4.97 ml (4.42 g, 61.33 mmol, 10.0 equiv.) of cyclopropyl carbinol in 25 ml of tetrahydrofuran was added 0.535 g (12.27 mmol, 2.0 equiv.) of sodium hydride dispersion (55% in mineral oil) in portions. The mixture was warmed to 55° C. and stirred for 1.5 h. The reaction mixture was poured into 200 ml of an ice/water mixture, the pH was adjusted to 8 by addition of saturated sodium bicarbonate solution, and the aqueous phase was extracted four times with 200 ml of ethyl acetate. The combined organic phases were washed twice with 25 ml of water, evaporated under reduced pressure and dried in a high vacuum. The thus obtained crude product was purified by chromatography on silica gel using a 1:2 v/v mixture of hexane and ethyl acetate as eluent to yield 3.32 g (6.07 mmol, 99.0% of theory) of the (3R,4R)-4-[4-(3-cyclopropylmethoxy-propoxy)-phenyl]-3-(quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil; MS: 547 (M+H)+.

Workup

  1. extractionthe aqueous phase was extracted four times with 200 ml of ethyl acetate
  2. washThe combined organic phases were washed twice with 25 ml of water
  3. customevaporated under reduced pressure
  4. customdried in a high vacuum
  5. customThe thus obtained crude product
  6. customwas purified by chromatography on silica gel using
  7. additiona 1:2 v/v mixture of hexane and ethyl acetate as eluent

Sources & evidence

ORD record
ord-e032a876c0e448f4b4e9f16ee8213fea
Source dataset
uspto-grants-2001_03
Patent number
US06197959B1

Reaction notes

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