Ethyl iodoacetate → HCID 57941516, compound

HRID 1438008Notes

Reaction equation

HRID 1438008 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[NH:10]1.I[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26]>CN(C)C=O>[CH2:28]([O:27][C:25](=[O:26])[CH2:24][N:10]1[C:11]2[C@@:12]3([CH3:22])[C:19]([CH3:21])([CH3:20])[C@H:15]([CH2:14][CH2:13]3)[C:16]=2[C:17](=[O:18])[N:9]1[C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])[CH3:29]

Participants

4

Reactant 2

HCID 12183Ethyl iodoacetateHCID 57941339(4s,7r)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941516HCID 57941516, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 256 mg, 0.84 mmol) and ethyl iodoacetate (500 μL, 4.22 mmol) in dimethylformamide (5 mL) was heated at 100° C. for 2 h. The solvent was evaporated, dichloromethane (75 mL) was added and the solution was washed with 1:1 water/aqueous sodium thiosulfate (25 mL). The aqueous layer was back-extracted with dichloromethane (25 mL) and the combined organic layers were washed with brine (25 mL). The solution was dried (magnesium sulfate), filtered, evaporated, purified using an ISCO 12 g column, eluting with 40-100% ethyl acetate/petroleum ether, and dried under high vacuum at 70° C. overnight to give [(4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-3-oxo-2,3,4,5,6,7-hexahydro-4,7-methano-indazol-1-yl]-acetic acid ethyl ester (130 mg, 40%) as a light yellow solid. APCI(+)-MS (M+H) 391.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (75 mL) was added
  3. washthe solution was washed with 1:1 water/aqueous sodium thiosulfate (25 mL)
  4. extractionThe aqueous layer was back-extracted with dichloromethane (25 mL)
  5. washthe combined organic layers were washed with brine (25 mL)
  6. dry with materialThe solution was dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. custompurified
  10. washeluting with 40-100% ethyl acetate/petroleum ether
  11. customdried under high vacuum at 70° C. overnight

Sources & evidence

ORD record
ord-955d018c72ca4e0b88c00c97f18b5224
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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