Citric Acid → ethyl 1-[(cis)-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazole-4-carboxylate

HRID 2366877Notes

Reaction equation

HRID 2366877 reaction equation
[CH3:1][CH:2]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH:24]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:22]=[CH:21]2)=[CH:16][CH:15]=1)[CH2:3][C:4]([NH:6][C:7]([O:9][CH:10]([CH3:12])[CH3:11])=[O:8])=O.[BH4-].[Na+].[Cl-].[Mg+2].[Cl-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.Cl>C(O)C.O.C(Cl)Cl>[CH3:1][C@H:2]1[CH2:3][C@@H:4]([NH:6][C:7]([O:9][CH:10]([CH3:12])[CH3:11])=[O:8])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N:20]3[CH:24]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:22]=[CH:21]3)[CH:18]=2)[NH:13]1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5360315Magnesium ChlorideHCID 67208063ethyl 1-(4-{[1-methyl-3-({[(1-methylethyl)oxy]carbonyl}amino)-3-oxopropyl]amino}phenyl)-1H-imidazole-4-carboxylate

Product 1

HCID 68162244ethyl 1-[(cis)-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazole-4-carboxylateYield 75%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of ethyl 1-(4-{[1-methyl-3-({[(1-methylethyl)oxy]carbonyl}amino)-3-oxopropyl]amino}phenyl)-1H-imidazole-4-carboxylate (for a preparation see intermediate 84) (5 g, 12.4 mmol) in ethanol (80 mL) was cooled to −15° C. The solution was treated with sodium borohydride (423 mg, 11.2 mmol) followed by a solution of magnesium chloride (2.78 g, 13.7 mmol) in water (15 mL) maintaining the temperature below −10° C. The mixture was stirred below 0° C. for 1 h then at room temperature for 1 h. The suspension formed was poured onto a stirred mixture of citric acid (4.89 g, 25.5 mmol), HCl (1M in water, 130 mL) and DCM (65 mL). The resulting mixture was stirred vigorously for 30 min and the layers were separated. The aqueous phase was basified by the addition of solid K2CO3 (CARE: gas evolved) and extracted with AcOEt (4×70 mL). The combined organic phases were washed with water then brine, dried over MgSO4 and concentrated in vacuo to give ethyl 1-[(cis)-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazole-4-carboxylate (3.6 g, 9.32 mmol, 75%) as a colourless foam which was used in the next step without further purification.

Workup

  1. temperaturemaintaining the temperature below −10° C
  2. waitat room temperature for 1 h
  3. customThe suspension formed
  4. stirringThe resulting mixture was stirred vigorously for 30 min
  5. customthe layers were separated
  6. additionThe aqueous phase was basified by the addition of solid K2CO3 (CARE: gas evolved)
  7. extractionextracted with AcOEt (4×70 mL)
  8. washThe combined organic phases were washed with water
  9. dry with materialbrine, dried over MgSO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-995cd5acd8814ab8b93430972e8aeabe
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…