Diisopropylamine → 3-Butyl-ureido-2-chloro-benzoic acid

HRID 1964920Notes

Reaction equation

HRID 1964920 reaction equation
C(NC(C)C)(C)C.O1CCCC1.C([Li])CCC.[NH2:18][C:19]1[C:20]([Cl:28])=[C:21]([CH:25]=[CH:26][CH:27]=1)[C:22]([OH:24])=[O:23].[N:29]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:30]=[O:31]>CCCCCC>[CH2:32]([NH:29][C:30](=[O:31])[NH:18][C:19]1[C:20]([Cl:28])=[C:21]([CH:25]=[CH:26][CH:27]=1)[C:22]([OH:24])=[O:23])[CH2:33][CH2:34][CH3:35]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 8110Butyl isocyanateHCID 4593153-Amino-2-chlorobenzoic acidHCID 178418339Butyllithium

Product 1

HCID 580875703-Butyl-ureido-2-chloro-benzoic acidYield 9.3%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To N,N-diisopropylamine (1.72 mL, 0.0122 mol) in tetrahydrofuran (12 mL, 0.14 mol), was added 1.6 M n-butyllithium in hexane (7.6 mL) at −78° C. under an atmosphere of nitrogen. After 30 minutes, 3-amino-2-chlorobenzoic acid (586, 1.00 g, 0.00583 mol) was added. After another 30 minutes, 1-isocyanatobutane (2.60 mL, 0.0233 mol) was added at −78° C. under an atmosphere of nitrogen and allowed to stir for two hours. The reaction mixture was warmed up to room temperature and stirred at room temperature for 30 minutes. The reaction was quenched with 1M HCl (aqueous) solution and extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with dichloromethane:methanol:acetic acid 40:2:1 to give the compound as an off-white solid (587, 147 mg, 9%).

Workup

  1. waitAfter another 30 minutes
  2. stirringstirred at room temperature for 30 minutes
  3. customThe reaction was quenched with 1M HCl (aqueous) solution
  4. extractionextracted with ethyl acetate twice
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. custompurified by silica gel column chromatography
  10. washeluting with dichloromethane:methanol:acetic acid 40:2:1

Sources & evidence

ORD record
ord-1eb1d68ce9f3469f8b1c1029bddf82c3
Source dataset
uspto-grants-2013_04
Patent number
US08415469B2

Reaction notes

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