Dimethylformamide → 3-(5-chloro-3-pyridyloxy)-N-(1-chloro-3-methylbut-1-yn-3-yl)butyramide

HRID 1374892Notes

Reaction equation

HRID 1374892 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]([CH2:13][CH3:14])[C:10](O)=O)[CH:5]=[N:6][CH:7]=1.CN(C)C=[O:18].C(Cl)(=O)C(Cl)=O.Cl.[Cl:27][C:28]#[C:29][C:30]([NH2:33])([CH3:32])[CH3:31]>ClCCl.CN(C)C1C=CN=CC=1.CCCCCC.C(OCC)(=O)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]([CH3:10])[CH2:13][C:14]([NH:33][C:30]([CH3:32])([CH3:31])[C:29]#[C:28][Cl:27])=[O:18])[CH:5]=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 210783581-Chloro-3-amino-3-methylbut-1-yne hydrochlorideHCID 210783782-(5-Chloro-3-pyridyloxy)butyric acid

Product 1

HCID 210784103-(5-chloro-3-pyridyloxy)-N-(1-chloro-3-methylbut-1-yn-3-yl)butyramide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

2-(5-Chloro-3-pyridyloxy)butyric acid (0.35 g; prepared as described in Stage 2 of Example 1) was stirred in dry dichloromethane (5 ml) containing N,N-dimethylformamide (0.1 ml) and treated dropwise with oxalyl chloride (0.145 ml) at ambient temperature. The solution was stirred for 0.5 hours and added in portions to a mixture of 1-chloro-3-amino-3-methylbut-1-yne hydrochloride (0.25 g; prepared as described below), dry triethylamine (0.68 ml) and 4-dimethylaminopyridine (0.01 g) in dry dichloromethane (5 ml) with stirring at ambient temperature. The mixture was stirred for 1 hour, stored for 18 hours, diluted with further dichloromethane, washed with aqueous sodium hydrogen carbonate, dried over magnesium sulphate and evaporated under reduced pressure to give an oil. The oil was fractionated by chromatography (silica:hexane/ethyl acetate 3:1 by volume) to give a solid that was recrystallised from hexane to give the required product as a colourless solid, 0.15 g, m.p. 78–82° C.

Workup

  1. stirringwith stirring at ambient temperature
  2. stirringThe mixture was stirred for 1 hour
  3. waitstored for 18 hours
  4. washwashed with aqueous sodium hydrogen carbonate
  5. dry with materialdried over magnesium sulphate
  6. customevaporated under reduced pressure
  7. customto give an oil
  8. customto give a solid
  9. customthat was recrystallised from hexane

Sources & evidence

ORD record
ord-46b9e99c369242969a0eb112830f4f40
Source dataset
uspto-grants-2007_01
Patent number
US07166621B2

Reaction notes

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