Trifluoroacetic acid → Benzamide, 2-((3-chloro-4-hydroxybenzoyl)amino)-N-(2-(2-methoxyphenyl)ethyl)-5-phenoxy-

HRID 2099963Notes

Reaction equation

HRID 2099963 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][C:36]=1[O:37]CC1C=CC(OC)=C(OC)C=1)[C:5]([NH:7][C:8]1[CH:26]=[CH:25][C:24]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:23][C:9]=1[C:10]([NH:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[O:21][CH3:22])=[O:11])=[O:6].C(O)(C(F)(F)F)=O.CCOC(C)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][C:36]=1[OH:37])[C:5]([NH:7][C:8]1[CH:26]=[CH:25][C:24]([O:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:23][C:9]=1[C:10]([NH:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[O:21][CH3:22])=[O:11])=[O:6]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 577968852-[[3-chloro-4-[(3,4-dimethoxyphenyl)methoxy]benzoyl]amino]-N-[2-(2-methoxyphenyl)ethyl]-5-phenoxy-benzamide

Product 1

HCID 11329787Benzamide, 2-((3-chloro-4-hydroxybenzoyl)amino)-N-(2-(2-methoxyphenyl)ethyl)-5-phenoxy-Yield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1E (27 mg, 0.04 mmol) in CH2Cl2 (2 mL) at 0° C. was treated with TFA (100 μL). The reaction was warmed to room temperature and stirred for three hours. The mixture was poured into EtOAc:buffer (1:1, pH 7, 40 mL) and the layers were separated. The organic layer was washed with pH 7 buffer (1×10 mL), dried (Na2SO4), filtered and concentrated to a yellow oil. The crude product was purified by preparative HPLC to afford 1F as a white solid (19 mg, 88%). 1H NMR (Acetone-d6) δ 8.80 (d, 1H, J=7.5 Hz), 8.17 (brs 1H), 8.01 (d, 1H, J=1.8 Hz), 7.81 (d, 1H, J=7.0 Hz), 7.45 (d, 1H, J=1.8 Hz), 7.36 (m, 2H), 7.15 (m, 5H), 6.97 (d, 1H, J=6.6 Hz), 6.89 (d, 1H, J=7.0 Hz), 6.79 (t, 1H, J=7.8 Hz), 3.77 (s, 3H), 3.64 (q, 2H, J=5.28 Hz), 2.93 (t, 2H, J=5.24 Hz). HPLC retention time=3.297 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). m/z=516.9 (M+H+).

Workup

  1. custombuffer (1:1, pH 7, 40 mL) and the layers were separated
  2. washThe organic layer was washed with pH 7 buffer (1×10 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a yellow oil
  6. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-19691cdee24645319ef3318953ac7de6
Source dataset
uspto-grants-2009_08
Patent number
US07569725B2

Reaction notes

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