Iodoacetamide → HCID 86583569, compound

HRID 1066630Notes

Reaction equation

HRID 1066630 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:16]2[CH:21]=[C:20]([CH:22]([CH3:24])[CH3:23])[C:19]([O:25]C(C)C)=[CH:18][C:17]=2[CH3:29])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:4]=1)#[N:2].B(Br)(Br)Br.C([O-])([O-])=O.[Cs+].[Cs+].I[CH2:41][C:42]([NH2:44])=[O:43].OS([O-])(=O)=O.[K+]>C(Cl)Cl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:16]2[CH:21]=[C:20]([CH:22]([CH3:23])[CH3:24])[C:19]([O:25][CH2:41][C:42](=[O:43])[NH2:44])=[CH:18][C:17]=2[CH3:29])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:4]=1)#[N:2]

Participants

7

Reactant 5

HCID 3727IodoacetamideHCID 10796Cesium carbonateHCID 25134Boron tribromideHCID 516920Potassium bisulfateHCID 86583570HCID 86583570, compound

Product 1

HCID 86583569HCID 86583569, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

The ethyl (RS)-(4-cyano-phenylamino)-(4-isopropoxy-5-isopropyl-2-methyl-phenyl)-acetate (921 mg, 2.34 mmol) obtained in Example 254.2 was dissolved in CH2Cl2 and cooled to −78° C. A 1M solution of BBr3 in CH2Cl2 (9.4 ml, 9.4 mmol) was slowly added dropwise. After 15 min. the reaction mixture was left to warm to 0° C. and was stirred for 1.5 h. at 0° C. Ice-water (30 ml) was added and the mixture was stirred for 10 min. at 0° C. The organic phase was separated and the aqueous phase was extracted with CH2Cl2. The organic phase was dried, filtered and concentrated. The crude product was dissolved in acetone, Cs2CO3 (918 mg, 2.76 mmol) and iodoacetamide (447 mg, 2.41 mmol) were added and the mixture was stirred for 6 h. at room temperature. A dilute aqueous solution of KHSO4 was added and the mixture was extracted with CH2Cl2. The organic phase was dried, filtered and concentrated, and the residue was purified by chromatography (SiO2, hexane/EtOAc 1:1=>1:2). There were obtained 704 mg, (73%) of ethyl (RS)-(4-cyano-phenylamino)-(4-carbamoylmethoxy-5-isopropyl-2-methyl-phenyl)-acetate as a colorless foam.

Workup

  1. temperatureto warm to 0° C.
  2. stirringthe mixture was stirred for 10 min. at 0° C
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with CH2Cl2
  5. customThe organic phase was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe crude product was dissolved in acetone
  9. stirringthe mixture was stirred for 6 h. at room temperature
  10. extractionthe mixture was extracted with CH2Cl2
  11. customThe organic phase was dried
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customthe residue was purified by chromatography (SiO2, hexane/EtOAc 1:1=>1:2)

Sources & evidence

ORD record
ord-d30ad03ee6b34dcd9cb4c546dcd706b6
Source dataset
uspto-grants-2001_06
Patent number
US06242644B1

Reaction notes

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