Hydrochloric Acid → HCID 178453693, compound

HRID 1628354Notes

Reaction equation

HRID 1628354 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 2˜3 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-5f02e39fb8af429a981d77f892f42fc8
Source dataset
uspto-grants-2014_07
Patent number
US08785648B1

Reaction notes

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