Acetic Acid → HCID 178423621, compound

HRID 2191218Notes

Reaction equation

HRID 2191218 reaction equation
C([OH:3])C.[F:4][C:5]([F:49])([F:48])[C:6]1[CH:7]=[C:8]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[CH2:9][N:10]([C:35]1[N:36]=[N:37][N:38]([CH3:40])[N:39]=1)[C@H:11]1[CH2:17][CH2:16][CH2:15][N:14]([CH2:18][C@H:19]2[CH2:24][CH2:23][C@H:22]([C:25]([O:27]C)=[O:26])[CH2:21][CH2:20]2)[C:13]2[C:29]([CH3:34])=[CH:30][C:31]([CH3:33])=[CH:32][C:12]1=2.[OH-].[Na+].C(O)(=O)C>O>[OH2:3].[F:47][C:44]([F:45])([F:46])[C:42]1[CH:41]=[C:8]([CH2:9][N:10]([C:35]2[N:36]=[N:37][N:38]([CH3:40])[N:39]=2)[C@@H:11]2[C:12]3[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH3:34])[C:13]=3[N:14]([CH2:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([C:25]([OH:27])=[O:26])[CH2:21][CH2:20]3)[CH2:15][CH2:16][CH2:17]2)[CH:7]=[C:6]([C:5]([F:4])([F:49])[F:48])[CH:43]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 702EthanolHCID 14798Sodium HydroxideHCID 178501098HCID 178501098, compound

Product 1

HCID 178423621HCID 178423621, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

Charge a 250 mL flask equipped with an overhead stirrer, with ethanol (100 mL), (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 (10.0 g, 15.32 mmoles) and NaOH (2 M, 15.0 mL, 30.0 mmoles). Warm the resulting mixture to about 40° C. and stir at that temperature for about 4 hrs. Allow the reaction mixture to cool to RT. Add acetic acid (2.7 mL, 45.4 mmoles) and warm to 40° C. Add water (40 mL) slowly over 2.5 h to provide a thick, white slurry. Continue heating for an additional 1.5 h and then allow the slurry to cool to RT. Collect the solid by filtration and sequentially wash the solid with ethanol:water (20 mL, 1:1), water (20 mL). Suspend the solid in water (70 mL); collect the solid via filtration; then wash the solid with water (2×20 mL). Repeat to the water slurry two additional times. Collect the resulting solid and dry at 60° C. to provide the titled compound as a white solid (6.1 g).

Workup

  1. additionCharge a 250 mL flask
  2. temperatureAllow the reaction mixture to cool to RT
  3. temperatureContinue heating for an additional 1.5 h
  4. temperatureto cool to RT
  5. customCollect the solid
  6. filtrationby filtration
  7. washsequentially wash the solid with ethanol
  8. customcollect the solid
  9. filtrationvia filtration
  10. washthen wash the solid with water (2×20 mL)
  11. customCollect the resulting solid
  12. customdry at 60° C.

Sources & evidence

ORD record
ord-1cbd0453022246d1ab284ad726459fbf
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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