Lithium Carbonate → HCID 18671667, compound

HRID 1057634Notes

Reaction equation

HRID 1057634 reaction equation
C1C=C[NH+]=CC=1.Br[Br-]Br.[CH2:10]([N:17]1[C:29]2[CH2:28][CH2:27][CH2:26][C:25](=[O:30])[C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([CH3:31])[CH:22]=2)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Br-].[Li+].C(=O)([O-])[O-].[Li+].[Li+]>C1COCC1.CN(C=O)C.CCCCCC>[CH2:10]([N:17]1[C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([OH:30])[C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([CH3:31])[CH:22]=2)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 11125Lithium CarbonateHCID 82050Lithium BromideHCID 11098227HCID 11098227, compound

Product 1

HCID 18671667HCID 18671667, compoundYield 42.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
75 °C

Procedure

Pyridinium bromide perbromide (11.9436 g, 0.0373 mol) is added to a mixture of 9-benzyl-6-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one (8.93 g, 0.0309 mol) in dry THF (42 mL) and dry DMF (30 mL) and the mixture is heated to 75° C. After stirring for 6 h, THF is removed under reduced pressure and the residue is partitioned between dichloromethane and brine. The combined organic layers are washed with dilute sodium thiosulfate/brine and the combined organic layers are dried over magnesium sulfate and concentrated under high vacuum to give an oil. Hexane is added to the oil and solids precipitated. These solids are upgraded by precipitation from dichloromethane/ethyl acetate/hexane and vacuum dried at room temperature. The soilds are combined with lithium bromide (3.5386 g, 0.041 mol), lithium carbonate (2.7427 g, 0.037 mol) and dry DMF (72 mL) and heated at 120° C. for 1.5 h. DMF then is removed under high vacuum and the mixture is partitioned between dichloromethane and water. The combined organic layers are washed with water and the aqueous layer is backwashed with dichloromethane. The combined organic layers are dried over sodium sulfate and concentrated to an oil. The oil is chromatographed on silica gel (300 mL) using ethyl acetate/heptane (30/70). The product fractions are rechromatographed on silica gel (200 mL) using ethyl acetate/heptane (10/90) to give 3.75 g (42%) of 9-benzyl-6-methyl-9H-carbazol-4-ol containing a significant amount of 9-benzyl-3-bromo-6-methyl-9H-carbazol-4-ol as an impurity. The material is purified by reduction of the bromide. 9-Benzyl-6-methyl-9H-carbazol-4-ol. The mixture (2.25 g, 0.0078 mol) is dissolved in dry THF (8 mL) is added to a slurry of lithium aluminum hydride (0.7604 g, 0.020 mol) in dry THF (42 mL). The mixture is stirred overnight at 75-80° C. The mixture then is cooled and water (0.8 mL) is added followed by 15% NaOH (0.8 mL) and then water (2.4 mL). The solids are removed by filtration and washed with THF. The filtrate is concentrated to dryness and the residue is chromatographed on silica gel (50 mL) using dichloromethane (100%). Recrystallization from dichloromethane/hexane give 1.48 g (52%) of the title compound; mp 160-161° C.; MS (ESI+) for C20H17NO m/z 288.2 (M+H)+; IR (drift) 3294, 1468, 1450, 1338, 1302, 1281, 1238, 1147, 1117, 790, 779, 746, 720, 714, 703 cm−1; 1H NMR (CDCl3) δ2.54, 5.29, 5.47, 6.57, 6.93, 7.12, 7.23, 8.12. Anal. Calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.51; H, 6.03; N, 4.94.

Workup

  1. customTHF is removed under reduced pressure
  2. customthe residue is partitioned between dichloromethane and brine
  3. washThe combined organic layers are washed with dilute sodium thiosulfate/brine
  4. dry with materialthe combined organic layers are dried over magnesium sulfate
  5. concentrationconcentrated under high vacuum
  6. customto give an oil
  7. customprecipitated
  8. customThese solids are upgraded by precipitation from dichloromethane/ethyl acetate/hexane and vacuum
  9. customdried at room temperature
  10. temperatureheated at 120° C. for 1.5 h
  11. customDMF then is removed under high vacuum
  12. customthe mixture is partitioned between dichloromethane and water
  13. washThe combined organic layers are washed with water
  14. dry with materialThe combined organic layers are dried over sodium sulfate
  15. concentrationconcentrated to an oil
  16. customThe oil is chromatographed on silica gel (300 mL)
  17. customThe product fractions are rechromatographed on silica gel (200 mL)

Sources & evidence

ORD record
ord-34ab353f2d834221ade71966efefeb5a
Source dataset
uspto-grants-2003_02
Patent number
US06514968B1

Reaction notes

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