Triethylamine → HCID 9799330, compound

HRID 1355080Notes

Reaction equation

HRID 1355080 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:30]=[C:29]([CH3:31])[O:28][N:27]=1.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:25][C:26]2[CH:30]=[C:29]([CH3:31])[O:28][N:27]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 661723-Amino-5-methylisoxazoleHCID 27627253-cyclopentyl-2-(3,4-dichlorophenyl)propanoic Acid

Product 1

HCID 9799330HCID 9799330, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 38A, 70.7 mg, 0.25 mmol) in oxalyl chloride (215 μL, 2.46 mmol) was cooled to 0° C. and then treated with 1 drop of dry N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 30 min and then stirred at 25° C. for 3 h. The reaction mixture was concentrated in vacuo to afford a yellow oil. This yellow oil was dissolved in a small amount of methylene chloride and then slowly added to a solution of 3-amino-5-methylisoxazole (48.3 mg, 0.49 mmol) and triethylamine (68 mL, 0.49 mmol) in methylene chloride (1.2 mL). The resulting reaction mixture was stirred at 25° C. for 14 h. The reaction mixture was concentrated in vacuo to remove methylene chloride. The resulting residue was diluted with ethyl acetate (100 mL) and then washed with a 10% aqueous hydrochloric acid solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-(5-methyl-isoxazol-3-yl)-propionamide (78.3 mg, 87%) as a yellow glass: mp 84–86° C.; FAB-HRMS m/e calcd for C18H20Cl2N2O2 (M+H)+ 367.0981, found 367.0982.

Workup

  1. stirringstirred at 25° C. for 3 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto afford a yellow oil
  4. customThe resulting reaction mixture
  5. stirringwas stirred at 25° C. for 14 h
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. customto remove methylene chloride
  8. additionThe resulting residue was diluted with ethyl acetate (100 mL)
  9. washwashed with a 10% aqueous hydrochloric acid solution
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5a442b01363e4bcaad0735cb3916685e
Source dataset
uspto-grants-2007_05
Patent number
US07223868B2

Reaction notes

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