HCID 22171031, compound → HCID 69196644, compound

HRID 2376239Notes

Reaction equation

HRID 2376239 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=3[Cl:21])[N:12]=[C:11]([CH2:22][CH2:23][C:24]([OH:26])=[O:25])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]>C1(C)C=CC=CC=1>[C:4]([O:25][C:24](=[O:26])[CH2:23][CH2:22][C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[N:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[N:12]=1)([CH3:9])([CH3:5])[CH3:3]

Participants

3

Reactant 1

HCID 22171031HCID 22171031, compound

Product 1

HCID 69196644HCID 69196644, compoundYield 196.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a 3-neck round bottom flask fitted with an air condenser was added 3-[5-(3,4-dichloro-phenyl)-1-(2,4-dichloro-phenyl)-1H-pyrazol-3-yl]-propionic acid (1.0 g, 2.3 mmol, 1.0 equiv) and toluene (23 mL) under nitrogen. The mixture was heated to 80° C. then N,N-dimethyl-di-tert-butylacetal (2.36 g, 11.6 mmol, 5.0 equiv) was added dropwise (neat). The reaction mixture was heated at 80° C. for 1 h then additional N,N-dimethyl-di-tert-butylacetal (2.36 g, 11.6 mmol, 5.0 equiv) was added. This mixture was stirred at 80° C. for 2 h then cooled to room temperature and partitioned between water (100 mL) and ether (100 mL). The organic layer was washed with 1 M sodium hydroxide (50 mL), water (50 mL) then brine (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude material was then purified by flash chromatography (20% ethyl acetate/hexanes) to afford the desired ester (1.1 g, >99%). HPLC: Rt=3.59 (Method A). MS (ESI): mass calculated for C22H20Cl4N2O2, 484.03; m/z found, 485.0 [M+H]+. 1H NMR (500 MHz, DMSO-d6): 7.81 (d, J=2.2 Hz, 1H), 7.65 (d, J=8.5 Hz, 1H), 7.61-7.59 (m, 2H), 7.48 (d, J=2.2 Hz, 1H), 7.05 (dd, J=8.2, 1.9 Hz, 1H), 6.71 (s, 1H), 2.87 (t, J=7.4 Hz, 2H), 2.61 (t, J=7.4 Hz, 2H), 1.38 (s, 9H).

Workup

  1. customTo a 3-neck round bottom flask fitted with an air condenser
  2. temperatureThe reaction mixture was heated at 80° C. for 1 h
  3. temperaturethen cooled to room temperature
  4. custompartitioned between water (100 mL) and ether (100 mL)
  5. washThe organic layer was washed with 1 M sodium hydroxide (50 mL), water (50 mL)
  6. dry with materialbrine (50 mL), dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was then purified by flash chromatography (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8011ef3ebd0e4ae0861f29aa6c59f54b
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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