3-Bromobenzoic acid → 3-bromo-N-(4-(trifluoromethoxy)phenyl)benzamide

HRID 629053Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.S(Cl)(Cl)=O.CCN(C(C)C)C(C)C.[F:24][C:25]([F:35])([F:34])[O:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1>C1(C)C=CC=CC=1.CCOC(C)=O.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:31][C:30]1[CH:32]=[CH:33][C:27]([O:26][C:25]([F:24])([F:34])[F:35])=[CH:28][CH:29]=1)=[O:7]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 3-bromobenzoic acid (10 g, 49.7 mmol), thionyl chloride (4.72 mL, 64.7 mmol), and DMF (1.5 mL) in toluene (80 mL) was stirred at 80° C. for 2 h. The mixture was cooled to 0° C., treated dropwise with DIPEA (19.11 mL, 109 mmol) followed by 4-trifluoromethoxyaniline (6.73 mL, 49.7 mmol) and the RM was allowed to warm to RT and stirred overnight. The mixture was diluted with EtOAc (150 mL), washed with 0.5 M HCl (2×100 mL), sat. NaHCO3 (2×100 mL) and brine (100 mL), dried over MgSO4 and the solvent was evaporated off under reduced pressure and the product was crystallized from n-heptane/EtOAc to afford the title compound. LC-MS (Condition 5) tR=1.37 min, m/z=360.1, 362.1 [M+H]+; 1H-NMR (400 MHz, MeOD) δ ppm 7.30 (d, J=8.80 Hz, 2H) 7.47 (t, J=7.95 Hz, 1H) 7.74-7.86 (m, 3H) 7.93 (d, J=7.82 Hz, 1H) 8.13 (s, 1H).

Workup

temperatureThe mixture was cooled to 0° C.
temperatureto warm to RT
stirringstirred overnight
washwashed with 0.5 M HCl (2×100 mL), sat. NaHCO3 (2×100 mL) and brine (100 mL)
dry with materialdried over MgSO4
customthe solvent was evaporated off under reduced pressure
customthe product was crystallized from n-heptane/EtOAc

Sources & evidence

ORD record: ord-c20f63867ffc42a79938fbc43a5fa39d
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315489B2

Reaction notes

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