Sodium Hydroxide → HCID 70873812, compound

HRID 2208893Notes

Reaction equation

HRID 2208893 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([N:15]([CH2:29][CH3:30])[C:16]2[C:17]([CH2:27][CH3:28])=[C:18]([CH:23]=[C:24]([Cl:26])[CH:25]=2)[C:19]([O:21]C)=[O:20])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1.CO>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([N:15]([CH2:29][CH3:30])[C:16]2[C:17]([CH2:27][CH3:28])=[C:18]([CH:23]=[C:24]([Cl:26])[CH:25]=2)[C:19]([OH:21])=[O:20])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide3×HCID 70873767HCID 70873767, compound

Product 1

HCID 70873812HCID 70873812, compoundYield 92.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of methyl 3-[(4-{[(tert-butoxy)carbonyl]amino}cyclohexyl)(ethyl)amino]-5-chloro-2-ethylbenzoate (156 mg, 0.36 mmol) in THF (4.0 ml) and MeOH (0.29 ml), was added a solution of 4M NaOH (aq) (2.7 ml, 10.7 mmol). The resulting solution was stirred at 50° C. for 17 hours. The reaction mixture was treated with 4M NaOH (aq) (0.5 ml, 2.0 mmol) and stirring was continued at 50° C. for 32 hours. The heat was removed and the reaction mixture was left to stir at room temperature for 65 hours. The reaction mixture was treated with 4M NaOH (aq) (1.0 ml, 4.0 mmol) and heated back up to 50° C. for 24 hours. The organic solvents were removed in-vacuo and the aqueous phase was treated with a solution of 0.5M citric acid (20 ml) to adjust the pH to 4/5. The product was extracted with ethyl acetate (3×25 ml). The combined organic phases were washed with brine (30 ml), dried (MgSO4), filtered and concentrated in-vacuo and then further dried on the high vac line for 4 hours to give the title compound (142 mg, 92%) as a white solid and a mixture of cis/trans isomers. LC-MS 98%, 5.49 min (7 minute LC-MS method), m/z=425.1, 427.1. 1H NMR shows a mixture of cis/trans isomers.

Workup

  1. stirringstirring
  2. waitwas continued at 50° C. for 32 hours
  3. customThe heat was removed
  4. waitthe reaction mixture was left
  5. stirringto stir at room temperature for 65 hours
  6. temperatureheated back up to 50° C. for 24 hours
  7. customThe organic solvents were removed in-vacuo
  8. additionthe aqueous phase was treated with a solution of 0.5M citric acid (20 ml)
  9. extractionThe product was extracted with ethyl acetate (3×25 ml)
  10. washThe combined organic phases were washed with brine (30 ml)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated in-vacuo
  14. customfurther dried on the high vac line for 4 hours

Sources & evidence

ORD record
ord-90270bbf342c43c4b92bc5cb9d2ba4a6
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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