Hydrochloric Acid → HCID 178453693, compound

HRID 2207263Notes

Reaction equation

HRID 2207263 reaction equation
C([O:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@H:10]([CH:13]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:14][NH:15][C:16]([C:18]2([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[CH2:20][CH2:19]2)=[O:17])[CH2:9][CH2:8]1)=[O:6])CC.[Li+].[OH-].[OH-].[Na+].Cl>C1COCC1.O.CO>[C:32]([O:31][C:29]([NH:28][CH:13]([C@H:10]1[CH2:9][CH2:8][C@H:7]([C:5]([OH:6])=[O:4])[CH2:12][CH2:11]1)[CH2:14][NH:15][C:16]([C:18]1([C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)[CH2:20][CH2:19]1)=[O:17])=[O:30])([CH3:35])([CH3:33])[CH3:34]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 178459587HCID 178459587, compound

Product 1

HCID 178453693HCID 178453693, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

cis-/trans-4-(1-tert-Butoxycarbonylamino-2-{[1-(4-chloro-phenyl)-cyclopropane-carbonyl]-amino}-ethyl)-cyclohexanecarboxylic acid propyl ester (1-9) (1.26 g, 0.00248 mol, 1 eq) was dissolved in THF (20 mL) and MeOH (10 mL) in a 250 mL RB flask LiOH (0.12 g, 0.00497 mol, 2 eq) in H2O (5 mL) was added to this solution. The reaction mixture was stirred at RT for 1 hour. NaOH (MW 40, 0.0075 mol, 3 eq) in H2O (5 mL) was added to the above reaction mixture. The reaction mixture was stirred at RT overnight. The reaction mixture was diluted with H2O. The pH was adjusted to 23 with 5% HCl while cooling with an ice-H2O bath. THF and MeOH were removed under vacuum. The residue was extracted with EtOAc (3×80 mL). The combined EtOAc extracts were washed with brine (1×80 mL), dried over Na2SO4 and solvent evaporated to dryness. The crude product was purified on silica gel column, eluting with MeOH/CH2Cl2 (1.25˜10%) to afford 0.28 g plus 0.23 g (less pure) (46% yield) of 1-10. The 1H NMR (DMSO-d6) data is depicted in FIG. 7.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. temperaturewhile cooling with an ice-H2O bath
  3. customTHF and MeOH were removed under vacuum
  4. extractionThe residue was extracted with EtOAc (3×80 mL)
  5. washThe combined EtOAc extracts were washed with brine (1×80 mL)
  6. dry with materialdried over Na2SO4 and solvent
  7. customevaporated to dryness
  8. customThe crude product was purified on silica gel column
  9. washeluting with MeOH/CH2Cl2 (1.25˜10%)

Sources & evidence

ORD record
ord-bdad0af9396f41458395d7753be6a556
Source dataset
uspto-grants-2016_06
Patent number
US09376423B2

Reaction notes

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