Tetrahydrofuran → N-[3,5-dibromo-4-[3-formyl-4-hydroxy-5-isopropylphenoxy]-2-methyl-phenyl]malonamic acid ethyl ester

HRID 1392555Notes

Reaction equation

HRID 1392555 reaction equation
C([CH:3]([C:7](Cl)=[O:8])[C:4](Cl)=[O:5])C.[NH2:10][C:11]1[CH:29]=[C:28]([Br:30])[C:14]([O:15][C:16]2[CH:17]=[C:18]([CH:25]([CH3:27])[CH3:26])[C:19]([OH:24])=[C:20]([CH:23]=2)[CH:21]=[O:22])=[C:13]([Br:31])[C:12]=1[CH3:32].CCN(CC)CC.C1C[O:43][CH2:42][CH2:41]1>>[CH2:42]([O:43][C:7](=[O:8])[CH2:3][C:4]([NH:10][C:11]1[CH:29]=[C:28]([Br:30])[C:14]([O:15][C:16]2[CH:17]=[C:18]([CH:25]([CH3:27])[CH3:26])[C:19]([OH:24])=[C:20]([CH:21]=[O:22])[CH:23]=2)=[C:13]([Br:31])[C:12]=1[CH3:32])=[O:5])[CH3:41]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 109209242-Ethylpropanedioyl dichlorideHCID 596784095-(4-Amino-2,6-dibromo-3-methylphenoxy)-2-hydroxy-3-isopropylbenzaldehyde

Product 1

HCID 59678444N-[3,5-dibromo-4-[3-formyl-4-hydroxy-5-isopropylphenoxy]-2-methyl-phenyl]malonamic acid ethyl esterYield 48%

Procedure

To a stirred solution of ethyl malonylchloride (7.2 μl, 0.056 mmol) and compound 5-(4-amino-2,6-dibromo-3-methylphenoxy)-2-hydroxy-3-isopropylbenzaldehyde of Part 8E (25 mg, 0.056 mmol) in THF (0.5 mL) was added Et3N (15.7 μl, 0.112 mmol) at 4° C. After 30 minutes stirring at room temperature, the reaction mixture was washed with NH4Cl (saturated aqueous solution) and the organic phase removed in vacuo. The water phase was extracted with CHC13 and the two phases were separated with a phase separator (IST). The organic phase was concentrated and the resulting residue was purified on column (silica gel, gradient elution: n-heptane/EtOAc from 1:0 to 7:3) to give 15 mg (48%) of N-[3,5-dibromo-4-[3-formyl-4-hydroxy-5-isopropylphenoxy]-2-methylphenyl]-malonamic acid ethyl ester as a light yellow residue.

Workup

  1. washthe reaction mixture was washed with NH4Cl (saturated aqueous solution)
  2. customthe organic phase removed in vacuo
  3. extractionThe water phase was extracted with CHC13
  4. customthe two phases were separated with a phase separator (IST)
  5. concentrationThe organic phase was concentrated
  6. customthe resulting residue was purified on column (silica gel, gradient elution: n-heptane/EtOAc from 1:0 to 7:3)

Sources & evidence

ORD record
ord-2ec52a87a3b8462da1296e706a36f27d
Source dataset
uspto-grants-2008_03
Patent number
US07342127B2

Reaction notes

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