Ethyl Acetate → HCID 67531325, compound

HRID 2388183Notes

Reaction equation

HRID 2388183 reaction equation
Br[CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[N:5][O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:21]([O:23][C:24](=[O:38])[CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1[O:36][CH3:37])[CH3:22].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>CN(C=O)C.[Cl-].[Na+].O>[CH3:37][O:36][C:29]1[CH:30]=[C:31]([O:34][CH3:35])[CH:32]=[CH:33][C:28]=1[CH2:27][N:26]([CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[N:5][O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:25][C:24]([O:23][CH2:21][CH3:22])=[O:38]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 19895532Ethyl 2-(2,4-dimethoxybenzylamino)acetateHCID 67529710Ethyl 4-(bromomethyl)-3-(4-methoxyphenyl)isoxazole-5-carboxylate

Product 1

HCID 67531325HCID 67531325, compoundYield 56.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Ethyl 4-(bromomethyl)-3-(4-methoxyphenyl)isoxazole-5-carboxylate (47.5 mmol) was dissolved in 100 mL of DMF. N-(2,4-dimethoxybenzyl)glycine ethyl ester (12.0 g, 47.5 mmol) and potassium carbonate (7.2 g, 41.6 mmol) were added, and the mixture was stirred at room temperature for 16 h. EtOAc (200 mL) and brine (200 mL) were added and the aqueous layer was extracted with additional EtOAc. The combined organic layer was washed with water and brine, and dried over MgSO4. After solvent was removed in vacuo, the crude was purified by flash chromatography (0-35% EtOAc/hexanes) to give 13.7 g of the title compound. 1H NMR (CDCl3, 200 MHz): δ=8.00 (d, 2H, J=8.8 Hz), 7.06-7.15 (m, 1H), 6.93 (d, 2H, J=8.8 Hz), 6.30-6.50 (m, 2H), 4.47 (q, 2H, J=7.4 Hz), 4.10-4.22 (m, 2H), 3.70-3.90 (m, 9H), 3.66 (s, 4H), 3.31 (s, 2H), 1.43 (t, 3H, J=7.0 Hz), 1.20-1.40 (m, 3H).

Workup

  1. extractionthe aqueous layer was extracted with additional EtOAc
  2. washThe combined organic layer was washed with water and brine
  3. dry with materialdried over MgSO4
  4. customAfter solvent was removed in vacuo
  5. customthe crude was purified by flash chromatography (0-35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-87542e1462cf4397a4e0e2fb8204c0f4
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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