3-Bromo-1-propanol → HCID 57941457, compound

HRID 1438006Notes

Reaction equation

HRID 1438006 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.Br[CH2:24][CH2:25][CH2:26][OH:27]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[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[N:10]1[CH2:24][CH2:25][CH2:26][OH:27]

Participants

5

Reactant 2

HCID 123083-Bromo-1-propanolHCID 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 57941457HCID 57941457, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 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; 355 mg, 1.17 mmol), tetrabutylammonium iodide (220 mg, 0.60 mmol) and 3-bromo-1-propanol (450 μL, 5.0 mmol) in dimethylformamide (4 mL) was heated at 100° C. for 21 h. Dichloromethane (100 mL), and the solution was washed with aqueous sodium thiosulfate (25 mL), and water (4×25 mL). The solution was dried (magnesium sulfate), and filtered. Silica gel was added and the solvent was evaporated. The resulting material was purified using an ISCO 12 g column, eluting with 0-5% methanol/ethyl acetate. Fractions containing the product were combined, evaporated, and dried under high vacuum at 95° C. overnight to give a gum that solidified on scratching. In this way was obtained (4S,7R)-2-(2,4-difluoro-phenyl)-1-(3-hydroxy-propyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (21 mg, 9%) as a light brown solid. APCI(+)-MS (M+H) 363.

Workup

  1. washDichloromethane (100 mL), and the solution was washed with aqueous sodium thiosulfate (25 mL), and water (4×25 mL)
  2. dry with materialThe solution was dried (magnesium sulfate)
  3. filtrationfiltered
  4. additionSilica gel was added
  5. customthe solvent was evaporated
  6. customThe resulting material was purified
  7. washeluting with 0-5% methanol/ethyl acetate
  8. additionFractions containing the product
  9. customevaporated
  10. customdried under high vacuum at 95° C. overnight
  11. customto give a gum that

Sources & evidence

ORD record
ord-ac24d889f4a445a58d121c47ac746d2f
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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