Dimethyl Sulfate → (4s,7r)-3-Methoxy-7,8,8-trimethyl-2-phenyl-4,5,6,7-tetrahydro-2h-4,7-methano-indazole

HRID 1437907Notes

Reaction equation

HRID 1437907 reaction equation
S(OC)(O[CH3:5])(=O)=O.[C:8]1([N:14]2[C:22](=[O:23])[C:21]3[C@@H:20]4[C:24]([CH3:26])([CH3:25])[C@@:17]([CH3:27])([CH2:18][CH2:19]4)[C:16]=3[NH:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>[OH-].[Na+].O>[CH3:5][N:15]1[C:16]2[C@@:17]3([CH3:27])[C:24]([CH3:26])([CH3:25])[C@H:20]([CH2:19][CH2:18]3)[C:21]=2[C:22](=[O:23])[N:14]1[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1.[CH3:5][O:23][C:22]1[N:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:15]=[C:16]2[C:21]=1[C@@H:20]1[C:24]([CH3:26])([CH3:25])[C@@:17]2([CH3:27])[CH2:18][CH2:19]1

Participants

6

Reactant 2

HCID 6497Dimethyl SulfateHCID 57941335(4s,7r)-2-Phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 2

HCID 57941522(4s,7r)-1,7,8,8-Tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 20%HCID 69022310(4s,7r)-3-Methoxy-7,8,8-trimethyl-2-phenyl-4,5,6,7-tetrahydro-2h-4,7-methano-indazoleYield 23%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

Dimethyl sulfate (0.4 mL, 4.1 mmol) was added to (4S,7R)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 1.00 g, 3.7 mmol) in 1 M NaOH (10 mL). The mixture was stirred at room temperature overnight and then diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried (magnesium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an RS-12 column, eluting with 0-16% ethyl acetate/hexanes to give (4S,7R)-1,7,8,8-tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (213 mg, 20%) as a white solid, (4S,7R)-3-methoxy-7,8,8-trimethyl-2-phenyl-4,5,6,7-tetrahydro-2H-4,7-methano-indazole (243 mg, 23%) as a yellow solid and unreacted starting material (243 mg, 24%).

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. custompurified
  7. washeluting with 0-16% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-89ddf294e8f544fb9e677e8f7d58e370
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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