Toluene → 3-(4-chloro-phenoxy)-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-prop-2-ynyloxy-propionamide

HRID 1818656Notes

Reaction equation

HRID 1818656 reaction equation
[CH2:1](Br)[C:2]#[CH:3].C1(C)C=CC=CC=1.[Cl:12][C:13]1[CH:39]=[CH:38][C:16]([O:17][CH2:18][CH:19]([OH:37])[C:20]([NH:22][CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]#[CH:34])=[C:27]([O:35][CH3:36])[CH:26]=2)=[O:21])=[CH:15][CH:14]=1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([O:17][CH2:18][CH:19]([O:37][CH2:3][C:2]#[CH:1])[C:20]([NH:22][CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]#[CH:34])=[C:27]([O:35][CH3:36])[CH:26]=2)=[O:21])=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 7842Propargyl bromideHCID 14798Sodium HydroxideHCID 117500513-(4-chloro-phenoxy)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxyphenyl)-ethyl]-propionamide

Product 1

HCID 444539523-(4-chloro-phenoxy)-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-prop-2-ynyloxy-propionamide

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

A 80% solution of propargyl bromide in toluene (1.6 g, 11 mmol) is added slowly at room temperature to a mixture of 3-(4-chloro-phenoxy)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-propionamide (3.5 g, 8.7 mmol), 30% sodium hydroxide solution (4.5 ml, 44 mmol) and catalytic amounts of tetrabutylammonium bromide (50 mg) in 30 ml of dichloromethane. The reaction is stirred for 16 hours at +40° C. Subsequently the mixture is evaporated and the residue is diluted with water and dichloromethane. The phases are separated and the aqueous phase is extracted three times with dichloromethane. The combined organic layer is washed with brine, dried over sodium sulfate and evaporated. The remaining oil is purified by chromatography on silica gel (ethyl acetate/hexane 1:1) to yield 3-(4-chloro-phenoxy)-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-prop-2-ynyloxy-propionamide (Compound E1.24).

Workup

  1. customSubsequently the mixture is evaporated
  2. additionthe residue is diluted with water and dichloromethane
  3. customThe phases are separated
  4. extractionthe aqueous phase is extracted three times with dichloromethane
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe remaining oil is purified by chromatography on silica gel (ethyl acetate/hexane 1:1)

Sources & evidence

ORD record
ord-53d754341a684dc680f3ccc42bb9b4e0
Source dataset
uspto-grants-2009_10
Patent number
US07601674B2

Reaction notes

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