1,2-Dichloroethane → Methyl 4-((4-methoxy-2-(trifluoromethyl)benzyl)carbamoyl)benzoate

HRID 923594Notes

Reaction equation

HRID 923594 reaction equation
[C:1]([O:12][CH3:13])(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([O-:8])=O)=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[CH3:37][O:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH2:44])=[C:41]([C:47]([F:50])([F:49])[F:48])[CH:40]=1>CN(C=O)C.C([O-])(O)=O.[Na+]>[CH3:37][O:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH:44][C:6]([C:5]2[CH:4]=[CH:3][C:2]([C:1]([O:12][CH3:13])=[O:11])=[CH:10][CH:9]=2)=[O:8])=[C:41]([C:47]([F:48])([F:49])[F:50])[CH:40]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 36144541,4-Benzenedicarboxylic acid, methyl esterHCID 43138648[4-Methoxy-2-(trifluoromethyl)phenyl]methanamine

Product 1

HCID 71076936Methyl 4-((4-methoxy-2-(trifluoromethyl)benzyl)carbamoyl)benzoateYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Prepared using General Procedure 6: A solution of mono-methyl terephthalate (315 mg, 1.75 mmol), HOBt (395 mg, 2.92 mmol), EDC (562 mg, 2.92 mmol) and DIEA (509 μL, 2.92 mmol) in DMF (10 mL) was stirred at room temperature. After 30 min, 4-methoxy-2-(trifluoromethyl)benzylamine (300 mg, 1.46 mmol) was added as a solution in DMF (2 mL). After stirring for 18 h, the reaction mixture was diluted with NaHCO3 and extracted with EA. The combined organic layers were dried (Na2SO4) and purified by chromatography (EA/hexanes) to provide 418 mg (78%) of methyl 4-((4-methoxy-2-(trifluoromethyl)benzyl)carbamoyl)benzoate INT-52. LCMS-ESI (m/z) calculated for C18H16F3NO4: 367; no m/z observed, tR=3.42 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.13-8.04 (m, 2H), 7.85-7.75 (m, 2H), 7.59 (d, J=8.6 Hz, 1H), 7.19 (d, J=2.7 Hz, 1H), 7.05 (dd, J=8.5, 2.7 Hz, 1H), 6.44 (s, 1H), 4.75 (d, J=5.9 Hz, 2H), 3.94 (s, 3H), 3.84 (s, 3H).

Workup

  1. customPrepared
  2. extractionextracted with EA
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. custompurified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-814822e078754dc6bf432da5af8fce36
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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