Ethyl oxoacetate → Ethyl 2-((4-chloro-2-methoxy-5-(1-methylcyclopropyl)phenyl)amino)acetate

HRID 588871Notes

Reaction equation

HRID 588871 reaction equation
[Cl:1][C:2]1[C:8]([C:9]2([CH3:12])[CH2:11][CH2:10]2)=[CH:7][C:5]([NH2:6])=[C:4]([O:13][CH3:14])[CH:3]=1.[C:15]([O:19][CH2:20][CH3:21])(=[O:18])[CH:16]=O.C([BH3-])#N.[Na+]>CO.CC(O)=O>[Cl:1][C:2]1[C:8]([C:9]2([CH3:12])[CH2:10][CH2:11]2)=[CH:7][C:5]([NH:6][CH2:16][C:15]([O:19][CH2:20][CH3:21])=[O:18])=[C:4]([O:13][CH3:14])[CH:3]=1

Participants

6

Reactant 3

HCID 70211Ethyl oxoacetateHCID 5003444Sodium cyanoborohydrideHCID 904558234-Chloro-2-methoxy-5-(1-methylcyclopropyl)aniline

Product 1

HCID 90456166Ethyl 2-((4-chloro-2-methoxy-5-(1-methylcyclopropyl)phenyl)amino)acetateYield 100.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a solution of 4-chloro-2-methoxy-5-(1-methylcyclopropyl)aniline (450 mg, 2.13 mmol) in MeOH (20 mL) at RT, AcOH (3 drops) and ethyl glyoxalate (326 mg, 3.19 mmol, 50% in toluene) were added. The mixture was stirred at RT for 2 h and then sodium cyanoborohydride (403 mg, 6.39 mmol) was added to the mixture. The resulting mixture was stirred at 50° C. for 16 h. The mixture was allowed to cool to RT, and partitioned between ethyl acetate and water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to afford the crude product (636 mg). ESI-MS m/z: 298.2[M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at 50° C. for 16 h
  2. temperatureto cool to RT
  3. custompartitioned between ethyl acetate and water
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f234432b94514c0daab7cd99b2ab5ce2
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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