Dimethyl Sulfate → HCID 69018306, compound

HRID 1437908Notes

Reaction equation

HRID 1437908 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+]>[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.[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

Participants

5

Reactant 2

HCID 6497Dimethyl Sulfate2×HCID 57941394HCID 57941394, compound2×

Product 2

HCID 57941504HCID 57941504, compoundYield 17%HCID 69018306HCID 69018306, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

Dimethyl sulfate (66 μL, 0.7 mmol) was added to (4R,7S)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 7; 185 mg, 0.7 mmol) in 1 M NaOH (5 mL). The mixture was vortexed and then heated with a heat gun for 30 sec., then shaken for 10 min, and extracted twice with dichloromethane. TLC indicated that the sodium hydroxide solution still contained starting material so a further quantity of dimethyl sulfate (150 μL, 1.6 mmol) was added and the mixture was vortexed, heated with a heat gun for 30 sec and then heated for 90 min at 100 degrees. The mixture was extracted with dichloromethane and the combined dichloromethane extracts were evaporated and purified by column chromatography, eluting initially with 50% ethyl acetate/hexanes and later with 12.5% methanol/ethyl acetate to give (4R,7S)-3-methoxy-7,8,8-trimethyl-2-phenyl-4,5,6,7-tetrahydro-2H-4,7-methano-indazole (70 mg, 35%) as a yellow solid, and (4R,7S)-1,7,8,8-tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (33 mg, 17%) as a white solid. APCI-MS (M+H) 283.

Workup

  1. temperatureheated with a heat gun for 30 sec
  2. extractionextracted twice with dichloromethane
  3. additionwas added
  4. temperatureheated with a heat gun for 30 sec
  5. temperatureheated for 90 min at 100 degrees
  6. extractionThe mixture was extracted with dichloromethane
  7. customthe combined dichloromethane extracts were evaporated
  8. custompurified by column chromatography
  9. washeluting initially with 50% ethyl acetate/hexanes and later with 12.5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-68508a6292f645eaa810deb763cf32e3
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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