Acetic Acid → HCID 68658794, compound

HRID 1931552Notes

Reaction equation

HRID 1931552 reaction equation
C(O)(=O)C.[NH2:5][C@:6]([CH3:59])([C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:7][O:8][C@@H:9]1[C@@:16]2([CH3:41])[C@@H:17]3[CH2:18][CH2:19][C@H:20]4[C:29]([C@@:12]3([CH2:13][O:14][CH2:15]2)[CH2:11][C@H:10]1[N:42]1[C:46]([C:47]2[CH:52]=[CH:51][C:50]([C:53]#[N:54])=[CH:49][CH:48]=2)=[N:45][CH:44]=[N:43]1)=[CH:28][CH2:27][C@:26]1([CH3:30])[C@:21]4([CH3:40])[CH2:22][CH2:23][C@@:24]([C@H:35]([CH3:39])[CH:36]([CH3:38])[CH3:37])([CH3:34])[C@H:25]1[C:31]([OH:33])=[O:32]>CO.[OH-].[OH-].[Pd+2]>[NH2:54][CH2:53][C:50]1[CH:49]=[CH:48][C:47]([C:46]2[N:42]([C@@H:10]3[CH2:11][C@:12]45[C:29]6[C@H:20]([CH2:19][CH2:18][C@H:17]4[C@@:16]([CH3:41])([CH2:15][O:14][CH2:13]5)[C@H:9]3[O:8][CH2:7][C@@:6]([NH2:5])([CH3:59])[C:55]([CH3:56])([CH3:58])[CH3:57])[C@:21]3([CH3:40])[C@:26]([CH3:30])([C@H:25]([C:31]([OH:33])=[O:32])[C@:24]([C@H:35]([CH3:39])[CH:36]([CH3:38])[CH3:37])([CH3:34])[CH2:23][CH2:22]3)[CH2:27][CH:28]=6)[N:43]=[CH:44][N:45]=2)=[CH:52][CH:51]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 59312674HCID 59312674, compound

Product 1

HCID 68658794HCID 68658794, compoundYield 77.8%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent2×

Procedure

Palladium hydroxide on carbon (10.6 mg, 0.015 mmol) and acetic acid (17 μl, 0.297 mmol) were added to a stirred solution of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-14-[5-(4-cyanophenyl)-1H-1,2,4-triazol-1-yl]-8-[(1R)-1,2-dimethylpropyl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (Example 168, 52.5 mg, 0.060 mmol) in methanol (3.0 ml). The reaction mixture was degassed (3×) and purged with hydrogen before being placed under a hydrogen balloon. After 6 hours, the hydrogen balloon was removed. The reaction mixture was degassed (2×), diluted with methanol, and filtered through a pad of Celite. The filtrate was evaporated under reduced pressure to give a colorless residue. The residue was dissolved in methanol and purified using a single HPLC run on a 30×150 mm Sunfire Prep C18 OBD 10 μm column by eluting with acetonitrile/water+0.1% TFA. The total flow rate was 20 ml/min and the HPLC method employed a 17 minute 20%-100% acetonitrile/water gradient followed by a 2 minute acetonitrile flush. The product fractions were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give the title compound (35.4 mg) as a white solid.

Workup

  1. customThe reaction mixture was degassed (3×)
  2. custompurged with hydrogen
  3. customthe hydrogen balloon was removed
  4. customThe reaction mixture was degassed (2×)
  5. additiondiluted with methanol
  6. filtrationfiltered through a pad of Celite
  7. customThe filtrate was evaporated under reduced pressure
  8. customto give a colorless residue
  9. custompurified
  10. washby eluting with acetonitrile/water+0.1% TFA
  11. waitThe total flow rate was 20 ml/min and the HPLC method employed a 17 minute
  12. wait20%-100% acetonitrile/water gradient followed by a 2 minute
  13. customacetonitrile flush
  14. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4caca49537af41bd80f408515b451be1
Source dataset
uspto-grants-2012_05
Patent number
US08188085B2

Reaction notes

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