Lithium hydroxide, monohydrate → 6-(Tert-butoxycarbonyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylic acid

HRID 1868470Notes

Reaction equation

HRID 1868470 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]2[CH:15]=[C:16]([C:18]([O:20]CC)=[O:19])[N:17]=[C:13]2[N:12]=[C:11]([CH3:23])[C:10]=1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].O[Li].O>C1COCC1.CO.O>[C:27]([O:26][C:24]([C:10]1[C:11]([CH3:23])=[N:12][C:13]2[N:14]([CH:15]=[C:16]([C:18]([OH:20])=[O:19])[N:17]=2)[C:9]=1[C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 469017436-Tert-butyl 2-ethyl 5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2,6-dicarboxylate

Product 1

HCID 579824816-(Tert-butoxycarbonyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylic acidYield 98.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 6-tert-butyl 2-ethyl 5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2,6-dicarboxylate (Example 54, Step 4, 3 g, 6.66 mmol) in THF (6 mL) and MeOH (2 mL) was added LiOH.H2O (0.42 g, 9.99 mmol) in H2O (2 mL). After 1 h, the reaction was quenched by 1N HCl till pH to 2. The organic volatiles were removed under reduced pressure and the residue was dissolved in EtOAc. The organic layer was washed with satd aq NH4Cl and brine prior to drying over MgSO4. Filtration, concentration under reduced pressure and recrystallization from 1:2 EtOAc/hexanes afforded 6-(tert-butoxycarbonyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylic acid (2.78 g, 90%) as a cream solid.

Workup

  1. customthe reaction was quenched by 1N HCl till pH to 2
  2. customThe organic volatiles were removed under reduced pressure
  3. dissolutionthe residue was dissolved in EtOAc
  4. washThe organic layer was washed with satd aq NH4Cl and brine
  5. dry with materialto drying over MgSO4
  6. filtrationFiltration, concentration
  7. customunder reduced pressure and recrystallization from 1:2 EtOAc/hexanes

Sources & evidence

ORD record
ord-83ed57e1453a4a49b5b896d20ca64f12
Source dataset
uspto-grants-2009_12
Patent number
US07635699B2

Reaction notes

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