Citric Acid → HCID 86669238, compound

HRID 2366882Notes

Reaction equation

HRID 2366882 reaction equation
CC([CH:5]([N:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][CH:21]([CH3:32])[CH2:22][C:23]([NH:25][C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27])=O)=[CH:16][CH:15]=2)[N:11]=[CH:10]1)[C:6]([O-:8])=[O:7])(C)C.[BH4-].[Na+].[Cl-].[Mg+2].[Cl-].C(O)(=O)[CH2:39][C:40]([CH2:45]C(O)=O)([C:42](O)=O)O.Cl>C(O)C.C(Cl)Cl>[CH3:32][C@H:21]1[CH2:22][C@@H:23]([NH:25][C:26]([O:28][CH:29]([CH3:30])[CH3:31])=[O:27])[C:16]2[C:17](=[CH:18][CH:19]=[C:14]([C:12]3[N:11]=[CH:10][N:9]([CH2:5][C:6]([O:8][C:40]([CH3:45])([CH3:42])[CH3:39])=[O:7])[CH:13]=3)[CH:15]=2)[NH:20]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5360315Magnesium ChlorideHCID 86762332HCID 86762332, compound

Product 1

HCID 86669238HCID 86669238, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of 1,1-dimethylethyl[4-(4-{[1-methyl-3-({[(1-methylethyl)oxy]carbonyl}amino)-3-oxopropyl]amino}phenyl)-1H-imidazol-1-yl]acetate (for a preparation see intermediate 89) (980 mg, 2.21 mmol) in ethanol (20 mLl) was cooled to −15° C. The solution was treated with sodium borohydride (75 mg, 1.98 mmol) followed by magnesium chloride (1M in water, 2.43 mL, 2.43 mmol) maintaining the temperature below −10° C. The reaction mixture 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 (1.06 g, 5.51 mmol), HCl (1M in water, 25 mL) and DCM (15 mL). The resulting mixture was stirred at room temperature for 30 min and the layers were separated. The aqueous layer 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 {(cis)-4-[2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazol-1-yl}acetate (645 mg, 1.505 mmol, 68%) as an orange oil.

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 at room temperature for 30 min
  5. customthe layers were separated
  6. additionThe aqueous layer was basified by the addition of solid K2CO3
  7. extractionthen was extracted with AcOEt (3×20 mL)
  8. washThe combined organic phases (DCM+EtOAc) were washed with water
  9. dry with materialbrine, dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 2% MeOH in DCM)

Sources & evidence

ORD record
ord-09069ab2fe1e497b84e2b1329a05be89
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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