Water → HCID 57941509, compound

HRID 1438005Notes

Reaction equation

HRID 1438005 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:9][C:10](=O)[CH2:11][N:12]1[C:20]2[C@@:19]3([CH3:24])[C:21]([CH3:23])([CH3:22])[C@H:16]([CH2:17][CH2:18]3)[C:15]=2[C:14](=[O:25])[N:13]1[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[F:33])C.O.[OH-].[Na+]>O1CCCC1>[F:33][C:27]1[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=1[N:13]1[C:14](=[O:25])[C:15]2[C@@H:16]3[C:21]([CH3:22])([CH3:23])[C@@:19]([CH3:24])([CH2:18][CH2:17]3)[C:20]=2[N:12]1[CH2:11][CH2:10][OH:9]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57941516HCID 57941516, compound

Product 1

HCID 57941509HCID 57941509, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of lithium aluminum hydride in tetrahydrofuran (Aldrich; 2 M; 80 μL; 0.16 mmol) was added to a solution of [(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 (Example 92; 57 mg, 0.15 mmol) in dry tetrahydrofuran (EMScience DriSolve; 700 μL) over 1 min, and the solution was stirred at room temperature for 18 h. Water (4 mL) was added and the mixture was stirred for 10 min. 2M aqueous sodium hydroxide solution (4 mL, 8 mmol) was added and the mixture was stirred for 10 min. The mixture was extracted with dichloromethane (50 mL) and the organic extract was dried (magesium sulfate), filtered, evaporated, and purified using an ISCO 4 g column, eluting with 0-10% methanol/ethyl acetate. Fractions containing the product were combined, evaporated, co-evaporated successively with methanol and ether, and then dried under high vacuum at 75° C. to give (4S,7R)-2-(2,4-difluoro-phenyl)-1-(2-hydroxy-ethyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (8 mg, 16%) as a white solid. ES(+)-MS (M+H) 349.

Workup

  1. stirringthe mixture was stirred for 10 min
  2. stirringthe mixture was stirred for 10 min
  3. extractionThe mixture was extracted with dichloromethane (50 mL)
  4. extractionthe organic extract
  5. dry with materialwas dried (magesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified
  9. washeluting with 0-10% methanol/ethyl acetate
  10. additionFractions containing the product
  11. customevaporated, co-evaporated successively with methanol and ether
  12. customdried under high vacuum at 75° C.

Sources & evidence

ORD record
ord-e3b5838f27384ca9b5164923cb06ebfe
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

Loading…