Hydrochloric Acid → HCID 178427879, compound

HRID 1438028Notes

Reaction equation

HRID 1438028 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:23][C:24]1[C:25]([O:30]C)=[N:26][CH:27]=[CH:28][CH:29]=1.C(O)C.Cl.C(=O)([O-])O.[Na+]>O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:20])([CH3:21])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:23][C:24]1[C:25]([OH:30])=[N:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 516892Sodium BicarbonateHCID 57941441HCID 57941441, compound

Product 1

HCID 178427879HCID 178427879, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (4R,7S)-2-(2,4-difluoro-phenyl)-1-(2-methoxy-pyridin-3-ylmethyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Example 113; 149 mg, 0.35 mmol), ethanol (440 μL) and concentrated aqueous hydrochloric acid (440 μL) was heated at 75° C. overnight, and then at ˜100° C. for 40 min. Water (10 mL) was added and the mixture was neutralized to pH 7-8 by the dropwise addition of saturated aqueous sodium hydrogen carbonate solution. The resulting mixture was extracted with dichloromethane (2×25 mL). The combined organic layers were washed with brine (10 mL), dried (magnesium sulfate), filtered, evaporated, purified using a Biotage 40S system, eluting with 3-4% methanol/dichcloromethane, and then dried in a vacuum overn for 3 days to give (4R,7S)-2-(2,4-difluoro-phenyl)-1-(2-hydroxy-pyridin-3-ylmethyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (108 mg, 75%) as an off-white solid. APCI(+)-MS (M+H) 412.

Workup

  1. extractionThe resulting mixture was extracted with dichloromethane (2×25 mL)
  2. washThe combined organic layers were washed with brine (10 mL)
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. custompurified
  7. washeluting with 3-4% methanol/dichcloromethane
  8. customdried in a vacuum overn for 3 days

Sources & evidence

ORD record
ord-c297c6619a1c46e3aee759b5de795941
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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