Sodium Hydroxide → HCID 178423619, compound

HRID 2191216Notes

Reaction equation

HRID 2191216 reaction equation
[F:1][C:2]([F:46])([F:45])[C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:6][N:7]([C:32]1[N:33]=[N:34][N:35]([CH3:37])[N:36]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([C:22]([O:24]C)=[O:23])[CH2:18][CH2:17]2)[C:10]2[C:26]([CH3:31])=[CH:27][C:28]([CH3:30])=[CH:29][C:9]1=2.[OH-].[Na+]>CO>[F:44][C:41]([F:42])([F:43])[C:39]1[CH:38]=[C:5]([CH2:6][N:7]([C:32]2[N:33]=[N:34][N:35]([CH3:37])[N:36]=2)[C@@H:8]2[C:9]3[CH:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[C:10]=3[N:11]([CH2:15][C@H:16]3[CH2:21][CH2:20][C@H:19]([C:22]([OH:24])=[O:23])[CH2:18][CH2:17]3)[CH2:12][CH2:13][CH2:14]2)[CH:4]=[C:3]([C:2]([F:1])([F:46])[F:45])[CH:40]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 178501098HCID 178501098, compound

Product 1

HCID 178423619HCID 178423619, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Charge a flask with (trans)-methyl 4-(((S)-5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methyl)cyclohexanecarboxylate (149 mg). Add MeOH (6 mL) and 1.0 N NaOH (3.0 mL). Heat the resulting mixture to about 60° C. Monitor the reaction via TLC. After about 7 hrs or when the starting ester has reacted, cool the mixture to about 0° C. and quench with 1 N HCl. Dilute the mixture with EtOAc (60 mL). Sequentially wash the mixture with water (20 mL), brine (20 mL) and dry over Na2SO4. Filter and concentrate the filtrate. Purify via flash chromatography with CH2Cl2. Remove the solvent to provide the title compound (125 mg) as a white solid.

Workup

  1. customMonitor the reaction via TLC
  2. temperaturecool the mixture to about 0° C.
  3. customquench with 1 N HCl
  4. additionDilute the mixture with EtOAc (60 mL)
  5. washSequentially wash the mixture with water (20 mL), brine (20 mL)
  6. dry with materialdry over Na2SO4
  7. filtrationFilter
  8. concentrationconcentrate the filtrate
  9. customPurify via flash chromatography with CH2Cl2
  10. customRemove the solvent

Sources & evidence

ORD record
ord-2e089a7425e74811b4e4e5d79daac3bc
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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