Ethyl chloroformate → HCID 69130224, compound

HRID 2253268Notes

Reaction equation

HRID 2253268 reaction equation
[CH3:1][O:2][C:3](=[O:34])[C:4]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31](=[O:33])[NH2:32])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)=[CH:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1.C([N-]C(C)C)(C)C.[Li+].Cl[C:44]([O:46][CH2:47][CH3:48])=[O:45]>C1COCC1>[CH3:1][O:2][C:3](=[O:34])[C:4]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:24]=[CH:25][C:26]([CH2:29][CH2:30][C:31]([NH:32][C:44]([O:46][CH2:47][CH3:48])=[O:45])=[O:33])=[CH:27][CH:28]=2)=[CH:18][CH:17]=1)=[CH:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 2724682Lithium diisopropylamideHCID 69130631HCID 69130631, compound

Product 1

HCID 69130224HCID 69130224, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

2-{4-[4-(2-Carbamoyl-ethyl)-phenoxy]-phenyl }-3-(3,5-dimethoxyphenyl)-acrylic acid methyl ester (7) was obtained as a byproduct in the synthesis of 3-(3,5-dimethoxy-phenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylmethyl)-phenoxy]-phenyl}-acrylic acid methyl ester, performed essentially as shown in PCT/US99/09982 (WO 99/58127). 7 (460 mg, 1.0 mmol) was taken up in dry THF (6 mL) and cooled to −78° C. To this solution, lithium diisopropyl amide (LDA) (2M, 0.55 mL, 1.1 mmol) was added and stirred for 10 min. Ethyl chloroformate (0.11 mL, 1.2 mmol) was added and stirred overnight at room temperature. The reaction was quenched with saturated aqueous ammonium chloride solution and ethyl acetate (50 mL) was added. The organic layer was washed with brine (2×20 mL), dried on anhydrous magnesium sulfate and evaporated under reduced pressure. The crude product was purified by silica gel chromatography and eluted with hexane-ethyl acetate (7:3). Yield: 264 mg, 49.8%.

Workup

  1. stirringstirred overnight at room temperature
  2. customThe reaction was quenched with saturated aqueous ammonium chloride solution and ethyl acetate (50 mL)
  3. additionwas added
  4. washThe organic layer was washed with brine (2×20 mL)
  5. dry with materialdried on anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography
  8. washeluted with hexane-ethyl acetate (7:3)

Sources & evidence

ORD record
ord-830ef66c1dd540d495bb59c68f6fccd8
Source dataset
uspto-grants-2008_01
Patent number
US07323496B2

Reaction notes

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