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

HRID 643232Notes

Reaction equation

HRID 643232 reaction equation
[CH2:1](Br)[C:2]#[CH:3].C1(C)C=CC=CC=1.[OH:12][CH:13]([CH:31]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:32])[C:14]([NH:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]#[CH:28])=[C:21]([O:29][CH3:30])[CH:20]=1)=[O:15].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[CH3:30][O:29][C:21]1[CH:20]=[C:19]([CH2:18][CH2:17][NH:16][C:14](=[O:15])[CH:13]([O:12][CH2:3][C:2]#[CH:1])[CH:31]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH3:32])[CH:24]=[CH:23][C:22]=1[O:25][CH2:26][C:27]#[CH:28]

Participants

7

Reactant 4

HCID 1140TolueneHCID 7842Propargyl bromideHCID 14798Sodium HydroxideHCID 592605822-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)ethyl]-3-phenyl-butyramide

Product 1

HCID 59260581N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-3-phenyl-2-prop-2-ynyloxy-butyramide

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

A 80% solution of propargyl bromide in toluene (1.2 g, 7.8 mmol) is added slowly at room temperature to a mixture of 2-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)ethyl]-3-phenyl-butyramide (2.4 g, 6.5 mmol), 30% sodium hydroxide solution (6.0 ml, 33 mmol) and catalytic amounts of tetrabutylammonium bromide (50 mg) in 25 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 N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-3-phenyl-2-prop-2-ynyloxy-butyramide (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-ac59e081a59742bdb0f46e650f1a7bd5
Source dataset
uspto-grants-2010_04
Patent number
US07700522B2

Reaction notes

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