Tetrahydrofuran → HCID 66725936, compound

HRID 1042145Notes

Reaction equation

HRID 1042145 reaction equation
C(OC(=O)[CH2:5][CH:6]1[S:10][C:9]([C:11]2[NH:12][C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([O:20][C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=2)=[CH:15][C:14]=3[O:31][CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[N:8][CH2:7]1)C.[CH3:39][Mg]Br.[Cl-].[NH4+].[O:44]1[CH2:48][CH2:47]CC1>CCCCCC.C(OCC)(=O)C.CO>[CH3:39][C:48]([OH:44])([CH3:47])[CH2:5][CH:6]1[S:10][C:9]([C:11]2[NH:12][C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([O:20][C:21]2[CH:22]=[CH:23][C:24]([S:27]([CH3:30])(=[O:28])=[O:29])=[CH:25][CH:26]=2)=[CH:15][C:14]=3[O:31][CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[N:8][CH2:7]1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 68090840HCID 68090840, compoundHCID 178418573HCID 178418573, compound5×

Product 1

HCID 66725936HCID 66725936, compoundYield 21%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

Ethyl(2-{5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-5-yl)acetate (400 mg) was dissolved in tetrahydrofuran (10 mL), methylmagnesium bromide (1M tetrahydrofuran solution, 3.6 mL) was added and the mixture was stirred under ice-cooling for 30 min, and then at room temperature for 1 hr. To the reaction solution was added methylmagnesium bromide (1M tetrahydrofuran solution, 1.4 mL), and the mixture was stirred at room temperature for 1 hr. Methylmagnesium bromide (1M tetrahydrofuran solution, 1.4 mL) was further added, and the mixture was stirred at room temperature for 1 hr. Methylmagnesium bromide (1M tetrahydrofuran solution, 1.4 mL) was further added, and the mixture was stirred at room temperature for 1 hr. Moreover, methylmagnesium bromide (1M tetrahydrofuran solution, 1.4 mL) was added, and the mixture was stirred at room temperature for 1 hr. To the reaction solution was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (methanol:ethyl acetate:hexane=0:50:50 to 20:80:0, volume ratio), then basic silica gel column chromatography (methanol:ethyl acetate:hexane=0:50:50 to 10:90:0, volume ratio) to give the title compound as a yellow oil (81 mg, yield 21%). The obtained yellow oil was crystallized from diethyl ether-hexane and recrystallized from ethyl acetate-hexane to give pale-yellow crystals.

Workup

  1. temperaturecooling for 30 min
  2. stirringthe mixture was stirred at room temperature for 1 hr
  3. stirringthe mixture was stirred at room temperature for 1 hr
  4. stirringthe mixture was stirred at room temperature for 1 hr
  5. stirringthe mixture was stirred at room temperature for 1 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained crude product

Sources & evidence

ORD record
ord-8fc89f0448dd4210b1159cfd12789f5f
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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