Water → HCID 59161192, compound

HRID 545515Notes

Reaction equation

HRID 545515 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]1[CH2:11][CH2:10][CH:9]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH2:8][C:7]2=1.[N+:23]([C:26]1[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=1[CH2:28]Br)([O-:25])=[O:24].O>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH2:28][C:27]1[CH:30]=[CH:31][CH:32]=[CH:33][C:26]=1[N+:23]([O-:25])=[O:24])[C:12]1[CH2:11][CH2:10][CH:9]([NH:17][C:18](=[O:22])[CH:19]([CH3:20])[CH3:21])[CH2:8][C:7]2=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 77569alpha-Bromo-2-nitrotolueneHCID 67196320HCID 67196320, compound

Product 1

HCID 59161192HCID 59161192, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Procedure

Suspend sodium hydride (60%, 120 mg, 3 mmol) in anhydrous DMF (2.5 mL) under nitrogen and cool in an ice bath. Slowly add N-(6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (prepare essentially as described in Preparation 4)(727 mg, 2.5 mmol) dissolved in DMF (8 mL). After 10 min remove ice bath and allow the reaction to warm to ambient temperature over 1 h. Add DMF (25 mL) and cool in a dry ice/acetone bath. Add dropwise a solution of 2-nitrobenzylbromide (648 mg, 3 mmol) in DMF (2.5 mL). Stir for 18 h, allowing to warm to ambient temperature. Pour into water and extract with ethyl acetate/diethyl ether (100 mL/50 mL). Separate and wash the aqueous portion with ethyl acetate (50 mL). Combine organics and wash with 1N hydrochloric acid (2×100 mL), brine (2×100 mL), dry (MgSO4), and concentrate in vacuo to obtain a yellow solid. Purify by flash chromatography eluting with dichloromethane and then a gradient up to 10% ethyl acetate/dichlorometbane to obtain 833 mg (79%) of a yellow solid.

Workup

  1. temperaturecool in an ice bath
  2. customas described in Preparation 4)(727 mg, 2.5 mmol)
  3. customAfter 10 min remove ice bath
  4. customthe reaction
  5. temperatureto warm to ambient temperature
  6. extractionextract with ethyl acetate/diethyl ether (100 mL/50 mL)
  7. customSeparate
  8. washwash the aqueous portion with ethyl acetate (50 mL)
  9. washCombine organics and wash with 1N hydrochloric acid (2×100 mL), brine (2×100 mL)
  10. dry with materialdry (MgSO4)
  11. concentrationconcentrate in vacuo
  12. customto obtain a yellow solid
  13. customPurify by flash chromatography
  14. washeluting with dichloromethane

Sources & evidence

ORD record
ord-7a806c49df284ee8945e923322bb63f5
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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