Citric Acid → HCID 68162260, compound

HRID 2366883Notes

Reaction equation

HRID 2366883 reaction equation
[CH3:1][CH:2]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[CH:22][N:23]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]=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.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:15]2[C:14](=[CH:19][CH:18]=[C:17]([C:20]3[N:21]=[CH:22][N:23]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]=3)[CH:16]=2)[NH:13]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5360315Magnesium ChlorideHCID 68162215HCID 68162215, compound

Product 1

HCID 68162260HCID 68162260, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of 1,1-dimethylethyl 3-[4-(4-{[1-methyl-3-({[(1-methylethyl)oxy]carbonyl}amino)-3-oxopropyl]amino}phenyl)-1H-imidazol-1-yl]propanoate (for a preparation see Intermediate 95) (1.53 g, 3.34 mmol) in ethanol (20 mL) was cooled to −15° C. then treated with sodium borohydride (114 mg, 3.0 mmol) followed by magnesium chloride (1M in water, 3.67 mL, 3.67 mmol) maintaining the temperature below −10° C. The mixture obtained was stirred at a temperature lower than 0° C. for 1 h then at room temperature for 1 h. The suspension formed was poured onto a stirred mixture of citric acid (1.6 g, 8.34 mmol), HCl (1M in water, 25 mL) and DCM (15 mL) and the mixture obtained was stirred at room temperature for 30 min. The layers were separated and the aqueous phase was basified by the addition of solid K2CO3 then was extracted with AcOEt (3×20 mL). The combined organic phases (DCM+EtOAc) were washed with water then brine dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 2% MeOH in DCM) gave 1,1-dimethylethyl 3-{(cis)-4-[2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazol-1-yl}propanoate (1.46 g, 3.30 mmol, 99%) as an orange oil.

Workup

  1. temperaturemaintaining the temperature below −10° C
  2. customThe mixture obtained
  3. waitat room temperature for 1 h
  4. customThe suspension formed
  5. customthe mixture obtained
  6. stirringwas stirred at room temperature for 30 min
  7. customThe layers were separated
  8. additionthe aqueous phase was basified by the addition of solid K2CO3
  9. extractionthen was extracted with AcOEt (3×20 mL)
  10. washThe combined organic phases (DCM+EtOAc) were washed with water
  11. dry with materialbrine dried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 2% MeOH in DCM)

Sources & evidence

ORD record
ord-b41fc7bd55e64d048ea5511db6a210ae
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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