Hydrochloric Acid → 3-(4-{4-[2-Dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-phenyl)-propionic acid methyl ester

HRID 748996Notes

Reaction equation

HRID 748996 reaction equation
Cl.Cl.[CH3:3][O:4][C:5](=[O:29])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([NH2:28])[C:23](=[O:27])[N:24]([CH3:26])[CH3:25])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1.CCN(C(C)C)C(C)C.[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1>C(Cl)Cl.C(O)(=O)C.C(OCC)(=O)C>[CH3:3][O:4][C:5](=[O:29])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([C:23](=[O:27])[N:24]([CH3:25])[CH3:26])[NH:28][S:45]([C:42]3[CH:43]=[CH:44][C:39]([CH3:49])=[CH:40][CH:41]=3)(=[O:47])=[O:46])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 691134593-{4-[4-(2-Amino-2-dimethylcarbamoyl-ethyl)-phenoxy]-phenyl}-propionic acid methyl ester hydrochloric acid salt

Product 1

HCID 691137573-(4-{4-[2-Dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-phenyl)-propionic acid methyl esterYield 56.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

Hydrochloride compound 23 (1.5 g, 3.69 mmol) was dissolved in CH2Cl2 (50 mL) and cooled to 0-5° C. N,N′-Diisopropylethylamine (1.28 mL, 7.74 mmol) was added to the above solution followed by addition of p-toluenesulfonyl chloride (0.58 g, 3.06 mmol) in small portions. The reaction mixture was then warmed up to room temperature and stirred overnight. The solvent was removed under reduced pressure and the residual oil was taken up in EtOAc (75 mL). The organic layer was washed with 2.0 M HCl (1×10 mL), water (1×50 mL), and brine (2×50 mL). The resulting EtOAc layer was dried and concentrated under reduced pressure to yield oil. Flash chromatography (hexanes:ethyl acetate—3:2 containing 1% acetic acid) yielded the desired sulfonamide 24 (0.9 g, 47%). 1H NMR (400 MHz, DMSO-d6): 7.54 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.0 Hz, 2H), 7.22 (d, J=8.8 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.39 (m, 1H), 3.58 (s, 3H), 2.72-2.92 (m, 4H), 2.69 (s, 3H), 2.57-2.64 (m, 4H), 2.47 (s, 3H), 2.35 (s, 3H).

Workup

  1. temperatureThe reaction mixture was then warmed up to room temperature
  2. customThe solvent was removed under reduced pressure
  3. washThe organic layer was washed with 2.0 M HCl (1×10 mL), water (1×50 mL), and brine (2×50 mL)
  4. dry with materialThe resulting EtOAc layer was dried
  5. concentrationconcentrated under reduced pressure
  6. customto yield oil

Sources & evidence

ORD record
ord-9c6840aae85c45ea8bf1d34cf83be389
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

Loading…