Dimethyl Sulfate → HCID 57941349, compound

HRID 1437930Notes

Reaction equation

HRID 1437930 reaction equation
S(OC)(O[CH3:5])(=O)=O.[I:8][C:9]1[CH:10]=[C:11]([N:15]2[C:23](=[O:24])[C:22]3[C@@H:21]4[C:25]([CH3:27])([CH3:26])[C@@:18]([CH3:28])([CH2:19][CH2:20]4)[C:17]=3[NH:16]2)[CH:12]=[CH:13][CH:14]=1>CO.[OH-].[Na+].O>[I:8][C:9]1[CH:10]=[C:11]([N:15]2[C:23](=[O:24])[C:22]3[C@@H:21]4[C:25]([CH3:27])([CH3:26])[C@@:18]([CH3:28])([CH2:19][CH2:20]4)[C:17]=3[N:16]2[CH3:5])[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 2

HCID 6497Dimethyl Sulfate2×HCID 57941451HCID 57941451, compound2×

Product 1

HCID 57941349HCID 57941349, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

Dimethyl sulfate (0.6 mL, 6.3 mmol) was added to a mixture of (4S,7R)-2-(3-iodo-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 18; 1.62 g, 4.1 mmol) in methanol (10 mL) and 1 M NaOH (20 mL). The mixture was stirred at room temperature overnight and then further portions of dimethyl sulfate (0.6 mL, 6.3 mmol) were added immediately, after 2 h, and after 5 h. The mixture was stirred at room temperature over the weekend, and it was then diluted with water and extracted with ethyl acetate (2×125 mL). The combined organic layers were washed with water (100 mL) and brine (100 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an RS-90 column, eluting with 0-100% ethyl acetate/hexanes to give (4S,7R)-2-(3-iodo-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (620 mg, 38%), as a white solid, (4S,7R)-2-(3-iodo-phenyl)-3-methoxy-7,8,8-trimethyl-4,5,6,7-tetrahydro-2H-4,7-methano-indazole (606 mg, 37%) as a yellow solid and unreacted starting material (140 mg, 9%). ES(+)-MS (M+H) 409.

Workup

  1. waitafter 5 h
  2. stirringThe mixture was stirred at room temperature over the weekend, and it
  3. extractionextracted with ethyl acetate (2×125 mL)
  4. washThe combined organic layers were washed with water (100 mL) and brine (100 mL)
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified
  9. washeluting with 0-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1805136d07d9431d8c6a29448dec93f4
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

Loading…