Ethyl bromoacetate → (3RS,4RS)-3-(1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1531483Notes

Reaction equation

HRID 1531483 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH: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)[CH:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][NH:43]3)=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49].[H-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[CH:16][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:18][CH:19]=2)[CH:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetate2×HCID 24758Sodium hydride2×HCID 69488852(3RS,4RS)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69486566(3RS,4RS)-3-(1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl esterYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 0.67 g (1.09 mmol) of (3RS,4RS)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-(1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester in 10 ml of absolute N,N-dimethylformamide was successively treated at 0° C. with 0.21 g (1.30 mmol, 1.2 equiv.) of ethyl bromoacetate and 0.057 g (1.30 g, 1.30 mmol, 1.2 equiv.) of sodium hydride dispersion (55% in mineral oil). The mixture was then stirred for 2 h at 80° C. Then 0.047 g (1.09 mmol, 1.0 equiv.) of sodium hydride suspension (55% in mineral oil) and 0.18 g (1.09 mmol, 1.0 equiv.) of ethyl bromoacetate was added, and the suspension was stirred for another 8 h at 80° C. Subsequently, the suspension was poured into 100 ml of an ice/water mixture and extracted three times with 50 ml of ethyl acetate. The combined organic phases were washed three times with 20 ml of water, dried over magnesium sulphate, evaporated under reduced pressure and dried in a high vacuum. The thus-obtained crude product was purified by chromatography on silica gel using a 19:1 mixture of dichloromethane and ethyl acetate as the eluent and yielded 0.25 g (0.36 mmol, 33.0% of theory) of (3RS,4RS)-3-(1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a light yellow oil; MS: 703 (M+H)+.

Workup

  1. stirringthe suspension was stirred for another 8 h at 80° C
  2. extractionextracted three times with 50 ml of ethyl acetate
  3. washThe combined organic phases were washed three times with 20 ml of water
  4. dry with materialdried over magnesium sulphate
  5. customevaporated under reduced pressure
  6. customdried in a high vacuum
  7. customThe thus-obtained crude product
  8. customwas purified by chromatography on silica gel using
  9. additiona 19:1 mixture of dichloromethane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-a259e53fdf7c428691fb2c131240f979
Source dataset
uspto-grants-2001_03
Patent number
US06197959B1

Reaction notes

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