Ethyl Acetate → HCID 67461620, compound

HRID 554865Notes

Reaction equation

HRID 554865 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][NH:6][C:7]([C:9]1[S:13][C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[N:11][C:10]=1[CH2:21][CH2:22]O)=[O:8].CCOC(C)=O.OI1(=O)C2C=CC=CC=2C(=O)O1>C(Cl)Cl>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]2[S:13][C:9]3[C:7](=[O:8])[N:6]([CH2:5][C:4]4[CH:24]=[CH:25][C:26]([O:28][CH3:29])=[CH:27][C:3]=4[O:2][CH3:1])[CH:22]=[CH:21][C:10]=3[N:11]=2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 3394961-Hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide2×HCID 67459250HCID 67459250, compound

Product 1

HCID 67461620HCID 67461620, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Mix 2-(4-chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid 2,4-dimethoxy-benzylamide (19.7 g, 45.5 mmol) with EtOAc (400 mL) and treat the resulting slurry with 1-hydroxy-1-oxo-1H-benzo[d][1,2]iodoxol-3-one (36.0 g, 57.8 mmol). Stir the mixture at 60° C. for 1.5 h. Add additional 1-hydroxy-1-oxo-1H-benzo[d][1,2]iodoxol-3-one (18.0 g, 28.9 mmol) and stir the mixture at 70° C. overnight. Cool the mixture to room temperature and then dilute with CH2Cl2 (600 mL). Filter the mixture and wash the solids with additional CH2Cl2 (3×500 mL). Wash the filtrate with NaHCO3 (4×300 mL) and water (300 mL). Dry the organic portion, filter, and concentrate in vacuo. Purify the crude material by flash chromatography, using 0.5% MeOH/CH2Cl2 as eluent, to give 13.1 g (70%) of the title compound as a light yellow-orange solid. 1H NMR (400 MHz, CDCl3) δ7.99 (d, 2H, J=8.1), 7.50 (d, 1H, J=7.4), 7.45 (d, 2H, J=8.8), 7.38 (d, 1H, J=8.8), 6.84 (d, 1H, J=6.4), 6.46 (m, 2H), 5.16 (s, 2H), 3.84 (s, 3H), 3.78 (s, 3H).

Workup

  1. stirringstir the mixture at 70° C. overnight
  2. temperatureCool the mixture to room temperature
  3. filtrationFilter the mixture
  4. washwash the solids with additional CH2Cl2 (3×500 mL)
  5. washWash the filtrate with NaHCO3 (4×300 mL) and water (300 mL)
  6. customDry the organic portion
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-4c20066332a540dfbb863b16923ec750
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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