Acetic Acid → HCID 178452616, compound

HRID 1424190Notes

Reaction equation

HRID 1424190 reaction equation
[C:1]([NH:8][C:9]1([C:18](O)=O)[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.ClC(OC(C)C)=O.C1(C)C=CC=CC=1.[Br:42][C:43]1[CH:44]=[C:45]([NH2:50])[C:46]([NH2:49])=[CH:47][CH:48]=1.C(O)(=O)C>CN(C)C=O>[Br:42][C:43]1[CH:48]=[CH:47][C:46]2[NH:49][C:18]([C:9]3([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[CH2:17][C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[CH2:10]3)=[N:50][C:45]=2[CH:44]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 1140TolueneHCID 7917Isopropyl chloroformateHCID 79724-MethylmorpholineHCID 3235934-Bromobenzene-1,2-diamineHCID 126815771066-00-7

Product 1

HCID 178452616HCID 178452616, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of N-Boc-2-aminoindane-2-carboxylic acid (3.30 g, 11.9 mmol) in N,N-dimethylformamide (15.0 mL) and 4-methylmorpholine (2.20 mL, 20.0 mmol) cooled to −20° C. was added a solution of isopropyl chloroformate in toluene (1.0 M, 20.0 mL, 20.0 mmol) dropwise over one hour. The mixture was stirred for an additional 60 minutes at −20° C. and then 4-bromo-1,2-benzenediamine (3.30 g, 17.6 mmol) was added. The reaction mixture was allowed to warm to room temperature for 18 hours. The solvent was evaporated, redissolved in ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The resulting residue was dissolved in acetic acid (20.0 mL, 352 mmol) and heated at 60° C. for 2 hours. After cooling, the solvent was removed in vacuo and then purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (3.05 g, 60%) as a brown solid.

Workup

  1. temperatureto warm to room temperature for 18 hours
  2. customThe solvent was evaporated
  3. dissolutionredissolved in ethyl acetate
  4. washwashed with water, saturated aqueous solution of sodium hydrogen carbonate, and brine
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. temperatureheated at 60° C. for 2 hours
  9. temperatureAfter cooling
  10. customthe solvent was removed in vacuo
  11. custompurified by silica gel column chromatography
  12. washeluting with a 0-100% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-f25aa67bd57840249e8182475880b105
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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