Sodium Chloride → [9-[(Cyclohexyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid, methyl ester

HRID 567367Notes

Reaction equation

HRID 567367 reaction equation
[CH:1]1([CH2:7][N:8]2[C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([OH:21])[C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][C:13]=3[C:22](=[O:24])[NH2:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:32][C:33]([O:35][CH3:36])=[O:34].[Na+].[Cl-]>CN(C=O)C.CCOC(C)=O.O>[CH:1]1([CH2:7][N:8]2[C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([O:21][CH2:32][C:33]([O:35][CH3:36])=[O:34])[C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][C:13]=3[C:22](=[O:24])[NH2:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 227381839-[(Cyclohexyl)methyl]-4-hydroxy-5-carbamoyl carbazole

Product 1

HCID 86756281[9-[(Cyclohexyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid, methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 9-[(cyclohexyl)methyl]-4-hydroxy-5-carbamoyl carbazole (60 mg, 0.186 mmol) and Cs2CO3 (150 mg; 0.460 mmol) in 2 mL of DMF was treated with methyl bromoacetate (0.023 mL; 0.242 mmol). The reaction was stirred for 2 hours at ambient temperature, then it was diluted with EtOAc and H2O (10 mL each). The aqueous layer was saturated with solid NaCl and extracted with EtOAc (2×10 mL). The combined organic layers were washed with H2O (2×25 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (elution with a gradient of 0% to 90% EtOAc/hexanes) followed by trituration with Et2O/EtOAc afforded 45 mg (0.114 mmol; 61%) of title compound as an off-white solid. MS (ES) m/e 395 (M+1), 378 (M+H−NH3), 453 (M+AcO−).

Workup

  1. extractionextracted with EtOAc (2×10 mL)
  2. washThe combined organic layers were washed with H2O (2×25 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the crude residue by flash chromatography on silica gel (
  7. washelution with a gradient of 0% to 90% EtOAc/hexanes)

Sources & evidence

ORD record
ord-93c3fd6ab91c491b8ab0d13d3cfd9716
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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