Isopropyl iodide → N-{(1RS,2SR)-2-hydroxy-2-(4-isopropoxyphenyl)-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-6,7-dihydro-5H-benzo[a][7]annulene-1-carboxamide

HRID 1610573Notes

Reaction equation

HRID 1610573 reaction equation
[OH:1][CH:2]([C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=1)[CH:3]([NH:18][C:19]([C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[CH2:31][CH2:30][CH2:29][CH:28]=[CH:27][C:26]=12)=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:17])([F:16])[CH:13]([F:15])[F:14])[CH:6]=1.C(=O)([O-])[O-].[K+].[K+].I[CH:46]([CH3:48])[CH3:47]>CN(C)C=O.O>[OH:1][CH:2]([C:32]1[CH:37]=[CH:36][C:35]([O:38][CH:46]([CH3:48])[CH3:47])=[CH:34][CH:33]=1)[CH:3]([NH:18][C:19]([C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[CH2:31][CH2:30][CH2:29][CH:28]=[CH:27][C:26]=12)=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:16])([F:17])[CH:13]([F:15])[F:14])[CH:6]=1

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 22262226N-{(1RS,2SR)-2-hydroxy-2-(4-hydroxyphenyl)-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-6,7-dihydro-5H-benzo[a][7]annulene-1-carboxamide

Product 1

HCID 22261385N-{(1RS,2SR)-2-hydroxy-2-(4-isopropoxyphenyl)-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-6,7-dihydro-5H-benzo[a][7]annulene-1-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{(1RS,2SR)-2-hydroxy-2-(4-hydroxyphenyl)-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-6,7-dihydro-5H-benzo[a][7]annulene-1-carboxamide (400 mg, 0.755 mmol) in N,N-dimethylformamide (15 ml) were added potassium carbonate (313 mg, 2.27 mmol) and 2-iodopropane (226 μl, 2.27 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1). Recrystallization from ethyl acetate-hexane gave the objective substance (287 mg, 66%).

Workup

  1. extractionextracted with ethyl acetate (100 ml×2)
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried (anhydrous magnesium sulfate)
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)
  6. customRecrystallization from ethyl acetate-hexane
  7. customgave the objective substance (287 mg, 66%)

Sources & evidence

ORD record
ord-d47c536af3214ac0b05c2bd314ed25d3
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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