Sodium hydride → Ccg-203778

HRID 538693

Reaction equation

HRID 538693 reaction equation
[CH3:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8](=[O:23])[N:9]([CH2:17][C:18](OCC)=[O:19])[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[H-].[Na+]>C1COCC1>[CH3:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]2[C:18](=[O:19])[CH2:17][N:9]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)[C:8]2=[O:23])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 70925838Ethyl 2-[3-(4-methylbenzyl)-1-p-tolylureido]acetate

Product 1

HCID 70688193Ccg-203778Yield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl bromoacetate (4.0 g, 30.0 mmol) was added to a solution of p-toluidine (2.1 g, 20 mmol) and sodium acetate (2.1 g, 26 mmol) in ethanol (26 mL). The resulting solution was warmed to 80° C. and stirred for 1 h before being cooled to room temperature. The reaction was quenched with water (20 mL) and the aqueous fraction extracted with ethyl acetate (3×20 mL). The organic fractions were combined, dried (MgSO4) and filtered, and the solvent was removed under reduced pressure. Silica chromatography (0-20% ethyl acetate/hexane) provided ethyl 2-(p-tolylamino)acetate as a pale oil (1.9 g, 50%). Ethyl 2-(p-tolylamino)acetate (260 mg, 1.4 mmol) was dissolved in toluene (5 mL). Methyl benzylisocyanate (200 mg, 1.4 mmol) was added to this solution. The mixture was heated to reflux and stirred for 5 h, until TLC analysis demonstrated that the reaction was complete. The reaction mixture was then cooled to room temperature, and the solvent was removed under reduced pressure. Silica chromatography (0-20% ethyl acetate/hexane) provided ethyl 2-[3-(4-methylbenzyl)-1-p-tolylureido]acetate as a pale oil (455 mg, 98%). Ethyl 2-[3-(4-methylbenzyl)-1-p-tolylureido]acetate (455 mg, 1.3 mmol) was dissolved in THF (10 mL) and added dropwise to a solution of NaH (68 mg, 2.8 mmol) in THF (10 mL) at 0° C. The reaction mixture was allowed to warm to room temperature slowly and stirred for 18 h before the reaction was quenched with water (5 mL). The aqueous fraction was then extracted with dichloromethane (3×20 mL). The organic fractions were combined, dried (MgSO4), and filtered, and the solvent was removed under reduced pressure. Column chromatography (0-20% ethyl acetate/hexane) provided 14 as a white solid.

Workup

  1. customwas quenched with water (5 mL)
  2. extractionThe aqueous fraction was then extracted with dichloromethane (3×20 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-2b835cd3d59c4e80ac3c02854eddf6e8
Source dataset
uspto-grants-2014_10
Patent number
US08865750B2

Linked notes

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