Diisopropylethylamine → [2-({1-[3,4-Difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-methanoyl}-aminooxy)-ethyl]-methyl-carbamic acid tert-butyl ester

HRID 2218479Notes

Reaction equation

HRID 2218479 reaction equation
[C:1]([O:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][O:11][NH2:12])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.FC1C([O:30][C:31](=O)[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[C:33]=2[NH:40][C:41]2[CH:46]=[CH:45][C:44]([I:47])=[CH:43][C:42]=2[CH3:48])=C(F)C(F)=C(F)C=1F>CN(C)C=O>[C:1]([O:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][O:11][NH:12][C:31]([C:32]1[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[C:33]=1[NH:40][C:41]1[CH:46]=[CH:45][C:44]([I:47])=[CH:43][C:42]=1[CH3:48])=[O:30])[CH3:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 233984843,4-Difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid pentafluorophenyl esterHCID 23398498tert-butyl N-[2-(aminooxy)ethyl]-N-methylcarbamate

Product 1

HCID 86591460[2-({1-[3,4-Difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-methanoyl}-aminooxy)-ethyl]-methyl-carbamic acid tert-butyl esterYield 62.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2-aminooxy-ethyl)-methyl-carbamic acid tert-butyl ester (0.63 g, 3.31 mmol) and diisopropylethylamine (0.6 mL, 3.44 mmol) in dimethylformamide (10 mL) was added 3,4-Difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid pentafluorophenyl ester (1.66 g, 2.99 mmol). The resultant reaction mixture was stirred 5 h at ambient temperature and concentrated under reduced pressure. The residue was diluted with ether (100 mL), washed with water (2×25 mL) and brine (2×25 mL), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography. Elution with dichloromethane afforded [2-({1-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-methanoyl}-aminooxy)-ethyl]-methyl-carbamic acid tert-butyl ester (1.05 g, 62%) as a white foam: 1 H NMR (400 MHz, DMSO-d6) δ 11.85 and 11.80 (br s, 1 H), 8.49 (br s, 1 H), 7.50 (s, 1 H), 7.39 (m, 1H), 7.35 (d, J=8.3 Hz, 1 H), 7.14 (m, 1 H), 6.46 (dd, J=7.8, 5.9 Hz, 1 H), 3.85 (br s, 2 H), 3.35 (br s, 2 H), 2.79 (br s, 3 H), 2.21 (s, 3 H), 1.36 and 1.33 (s, 9 H); 19F NMR (376 MHz, DMSO-d6) δ −132.9, −143.3 (d, J=17.7 Hz); MS (APCI+)=562.1.

Workup

  1. customThe resultant reaction mixture
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with ether (100 mL)
  4. washwashed with water (2×25 mL) and brine (2×25 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washElution with dichloromethane

Sources & evidence

ORD record
ord-b2fc141bcb8f4ae389a91abcb733d535
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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