Dimethylamine, hydrochloride → Ethyl 4-[4-(difluoromethyl)phenoxy]-2-[(dimethylamino)-carbonyl]-1-benzofuran-6-carboxylate

HRID 1643767Notes

Reaction equation

HRID 1643767 reaction equation
[F:1][CH:2]([F:27])[C:3]1[CH:26]=[CH:25][C:6]([O:7][C:8]2[C:13]3[CH:14]=[C:15]([C:17](O)=[O:18])[O:16][C:12]=3[CH:11]=[C:10]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:9]=2)=[CH:5][CH:4]=1.[CH3:28][N:29](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:30].F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.CNC>CN(C=O)C.O>[F:1][CH:2]([F:27])[C:3]1[CH:26]=[CH:25][C:6]([O:7][C:8]2[C:13]3[CH:14]=[C:15]([C:17]([N:29]([CH3:30])[CH3:28])=[O:18])[O:16][C:12]=3[CH:11]=[C:10]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:9]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595601994-[4-(Difluoromethyl)phenoxy]-6-(ethoxycarbonyl)-1-benzofuran-2-carboxylic acid

Product 1

HCID 59560302Ethyl 4-[4-(difluoromethyl)phenoxy]-2-[(dimethylamino)-carbonyl]-1-benzofuran-6-carboxylateYield 74.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-[4-(difluoromethyl)phenoxy]-6-(ethoxycarbonyl)-1-benzofuran-2-carboxylic acid (300 mg, 0.80 mmol) in DMF (10 mL) was added HATU (606 mg, 1.59 mmol), DIEA (515 mg, 4.0 mmol) and the solution was stirred at 0° C. for 15 min. Dimethylamine hydrochloride (97.5 mg, 1.20 mmol) was added and the solution was warmed gradually to room temperature and stirred for 14 h. Water was added to the reaction and the product was extracted with CHCl3. The combined organic layers were washed with water twice, dried over MgSO4, and concentrated. The product was purified via gradient silica gel chromatography using CHCl3/MeOH (100/0 to 95/5) to give the title compound (240 mg, 70%) as a light yellow solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.38 (t, J=7.16 Hz, 3 H) 3.13 (s, 3 H) 3.32 (s, 3 H) 4.38 (q, J=7.16 Hz, 2 H) 6.64 (t, J=56.61 Hz, 1 H) 7.09 (d, J=8.48 Hz, 2 H) 7.16 (s, 1 H) 7.50 (d, J=8.48 Hz, 2 H) 7.55 (s, 1 H) 8.05 (s, 1 H).

Workup

  1. temperaturethe solution was warmed gradually to room temperature
  2. stirringstirred for 14 h
  3. extractionthe product was extracted with CHCl3
  4. washThe combined organic layers were washed with water twice
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe product was purified via gradient silica gel chromatography

Sources & evidence

ORD record
ord-761727bbfa9b438ba00a24a665abac5b
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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