Cesium carbonate → HCID 23405924, compound

HRID 489120Notes

Reaction equation

HRID 489120 reaction equation
[CH3:1][O:2][C:3](=[O:32])[CH2:4][O:5][C:6]1[CH:14]=[C:13]2[CH2:15][CH2:16][CH2:17][C:12]2=[C:11]2[C:7]=1[CH:8]=[C:9]([CH3:31])[N:10]2[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[S:26][C:27]([Br:30])=[CH:28][CH:29]=1.CC1[NH:35]C2C(C=1)=C(OC)C=C1CCCC=21.[H-].[Na+].BrC1SC(C2C=CC=CC=2CBr)=CC=1.B(Br)(Br)Br.[C:68](=[O:71])(O)[O-].[Na+].[C:73](=[O:76])([O-])[O-].[Cs+].[Cs+].BrCC(OC)=O>CN(C)C=O.O.CO>[CH3:1][O:2][C:3](=[O:32])[CH2:4][O:5][C:6]1[CH:14]=[C:13]2[CH2:15][CH2:16][CH2:17][C:12]2=[C:11]2[C:7]=1[C:8]([C:68](=[O:71])[C:73]([NH2:35])=[O:76])=[C:9]([CH3:31])[N:10]2[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[S:26][C:27]([Br:30])=[CH:28][CH:29]=1

Participants

12

Reactant 8

HCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 25134Boron tribromideHCID 60984Methyl bromoacetateHCID 516892Sodium BicarbonateHCID 22268687HCID 22268687, compoundHCID 22268694HCID 22268694, compoundHCID 23405923HCID 23405923, compound

Product 1

HCID 23405924HCID 23405924, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Preparation of 2-[(1-[2-(5-bromothiophen-2-yl)benzyl]-2-methyl-1,6,7,8-tetrahydrocyclopent[g]indol-4-yl)oxy]acetic acid methyl ester. To a solution of 2-methyl-4-methoxy-1,6,7,8-tetrahydrocyclopent[g]indole (517 mg, 2.57 mmol) in N,N-dimethylformamide (10 mL) was added a dispersion of 60% sodium hydride in mineral oil (120 mg). After gas evolution had ceased, a solution of 2-bromo-5-(2-bromomethylphenyl)thiophene (975 mg, 3.85 mmol) in N,N-dimethylformamide (5 mL) was added over 2-3 min. The resulting mixture was stirred for 108 h, diluted with water, and extracted with a 1:1 mixture of ether/hexane. The organic phase was washed twice with water, concentrated in vacuo, dissolved in methylene chloride, and passed through a pad of silica gel. The filtrate was concentrated in vacuo and the residue dissolved in methylene chloride (10 mL), cooled to 0° C., and treated with boron tribromide (0.11 mL, 2.0 mmol). The mixture was allowed to warm to room temperature and stir for 2 h. Methanol (2 mL) was added followed by saturated sodium bicarbonate solution (˜30 mL). The resulting mixture was extracted twice with methylene chloride. The combined organic layers were dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was immediately dissolved in N,N-dimethylformamide (5 mL) and treated with cesium carbonate (490 mg, 1.5 mmol) and methyl bromoacetate (0.14 mL, 1.5 mmol) at room temperature for 18 h. The mixture was diluted with water, stirred for 30 min, and the resulting solid collected via vacuum filtration. Chromatography (silica gel, hexane/methylene chloride) provided 187 mg (14%) of the title compound as a beige solid. 1H NMR (CDCl3) δ 7.36 (d, J=7 Hz, 1H), 7.23 (t, J=8 Hz, 1H), 7.13 (t, J=8 Hz, 1H), 7.10 (d, J=4 Hz, 1H), 6.86 (d, J=4 Hz, 1H), 6.45 (s, 1H), 6.33 (s, 1H), 6.32 (d, J=7 Hz, 1H), 5.41 (s, 2H), 4.75 (s, 2H), 3.81 (s, 3H), 2.85 (m, 4H), 2.22 (s, 3H), 2.01 (quintet, J=7 Hz, 2H); MS ES+ m/e 509, 511 (p+1).

Workup

  1. extractionextracted with a 1:1 mixture of ether/hexane
  2. washThe organic phase was washed twice with water
  3. concentrationconcentrated in vacuo
  4. dissolutiondissolved in methylene chloride
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionthe residue dissolved in methylene chloride (10 mL)
  7. temperatureto warm to room temperature
  8. stirringstir for 2 h
  9. extractionThe resulting mixture was extracted twice with methylene chloride
  10. dry with materialThe combined organic layers were dried (magnesium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. dissolutionThe residue was immediately dissolved in N,N-dimethylformamide (5 mL)
  14. stirringstirred for 30 min
  15. filtrationthe resulting solid collected via vacuum filtration

Sources & evidence

ORD record
ord-8aae9521cb284cb8989c22af6acd75ca
Source dataset
uspto-grants-2005_12
Patent number
US06974831B2

Reaction notes

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