Hydrochloric Acid → HCID 178453818, compound

HRID 1628356Notes

Reaction equation

HRID 1628356 reaction equation
C([O:4][C:5]([CH:7]1[CH2:12][CH2:11][CH:10]([CH:13]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:14](=[O:27])[NH:15][CH2:16][C:17]2([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:19][CH2:18]2)[CH2:9][CH2:8]1)=[O:6])CC.[OH-].[Na+].Cl>CO.C1COCC1.O>[C:32]([O:31][C:29]([NH:28][CH:13]([C:14](=[O:27])[NH:15][CH2:16][C:17]1([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[CH2:18][CH2:19]1)[C@H:10]1[CH2:11][CH2:12][C@H:7]([C:5]([OH:6])=[O:4])[CH2:8][CH2:9]1)=[O:30])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86762557HCID 86762557, compound

Product 1

HCID 178453818HCID 178453818, compoundYield 34.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

4-(tert-Butoxycarbonylamino-{[1-(4-chloro-phenyl)-cyclopropylmethyl]-carbamoyl}-methyl)-cyclohexanecarboxylic acid propyl ester (2-2) (1.77 g, 0.0035 mol, 1 eq) was dissolved in MeOH (20 mL) and THF (6 mL). NaOH (0.42 g, 0.0105 mol, 3 eq) in H2O (2 mL) was added. The reaction mixture was stirred at RT and monitored by TLC and LC/MS. After stirring at RT for 20 hours, the reaction mixture was diluted with H2O. The pH was adjusted to pH=3 with 10% HCl while cooling with ice-H2O bath. The aqueous was extracted with EtOAc (3×60 mL). The combined EtOAc was washed with brine. After drying over Na2SO4 and filtration, the filtrate was concentrated under vacuum to dryness. The crude product was purified on silica gel column, eluted with 2% MeOH/CH2Cl2 to give trans-4-(tert-Butoxycarbonylamino-{[1-(4-chloro-phenyl)-cyclopropylmethyl]-carbamoyl}-methyl)-cyclohexanecarboxylic acid 0.56 g (2-3) (34.4%). 1H NMR (DMSO-d6) data is depicted in FIG. 19.

Workup

  1. stirringAfter stirring at RT for 20 hours
  2. temperaturewhile cooling with ice-H2O bath
  3. extractionThe aqueous was extracted with EtOAc (3×60 mL)
  4. washThe combined EtOAc was washed with brine
  5. dry with materialAfter drying over Na2SO4 and filtration
  6. concentrationthe filtrate was concentrated under vacuum to dryness
  7. customThe crude product was purified on silica gel column
  8. washeluted with 2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-8a9e490175904b7d83ff55944e0e2672
Source dataset
uspto-grants-2014_07
Patent number
US08785648B1

Reaction notes

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