Hydrochloric Acid → 2-{4-[4-(2,4-Dioxothiazolidin-5-ylmethyl)-phenoxy]-phenyl}-3-p-tolylacrylic acid methyl ester

HRID 2238259Notes

Reaction equation

HRID 2238259 reaction equation
[O:1]=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:33]=[CH:32][C:12]([O:13][C:14]3[CH:19]=[CH:18][C:17]([C:20](=[CH:24][C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=4)[C:21]([OH:23])=[O:22])=[CH:16][CH:15]=3)=[CH:11][CH:10]=2)[S:3]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:44]=2N=N1.C(N(CC)CC)C.C[O-].[Na+].Cl>ClCCl.CO>[CH3:44][O:22][C:21](=[O:23])[C:20]([C:17]1[CH:16]=[CH:15][C:14]([O:13][C:12]2[CH:11]=[CH:10][C:9]([CH2:8][CH:4]3[S:3][C:2](=[O:1])[NH:6][C:5]3=[O:7])=[CH:33][CH:32]=2)=[CH:19][CH:18]=1)=[CH:24][C:25]1[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10942334Sodium MethoxideHCID 72556533HCID 72556533, compound

Product 1

HCID 743888392-{4-[4-(2,4-Dioxothiazolidin-5-ylmethyl)-phenoxy]-phenyl}-3-p-tolylacrylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 41 (0.1 g, 0.218 mmol) and BOP [Castro's Reagent, Benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate] (0.144 g, 0.326 mmol) in 5 mL dichloromethane was added triethylamine (0.067 mL, 0.477 mmol). The mixture was stirred for 1 h, and then sodium methoxide (0.5 M solution in methanol, 0.07 mL, 0.035 mmol) was added with 5 mL MeOH. The reaction was allowed to stir at room temperature for 16 h. 5% HCl was added to pH 0 and the mixture was extracted with 25 mL dichloromethane three times. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was loaded onto silica gel column as a solution in dichloromethane. The product was eluted with hexanes-ethyl acetate (3:2). Fractions were concentrated in vacuum to a white solid (0.037 g, 36.4%). 1H NMR (400 MHz, DMSO-d6) δ 12.05 (br s, 1H), 7.75 (s, 1H), 7.30 (d, J=8.8 Hz, 2H), 7.18 (d, J=8.8 Hz, 2H), 7.06 (d, J=8.0 Hz, 2H), 7.02 (d, J=8.8 Hz, 2H), 6.99 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.0 Hz, 2H), 4.91 (dd, J=4.8 and 9.6 Hz, 1H), 3.72 (s, 3H), 3.39 (dd, J=4.0 and 13.6 Hz, 1H), 3.13 (dd, J=9.2 and 14.0 Hz, 1H), 2.25 (s, 3H).

Workup

  1. stirringto stir at room temperature for 16 h
  2. extractionthe mixture was extracted with 25 mL dichloromethane three times
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washThe product was eluted with hexanes-ethyl acetate (3:2)
  8. concentrationFractions were concentrated in vacuum to a white solid (0.037 g, 36.4%)

Sources & evidence

ORD record
ord-f2a201a3b55c4cc197d5e0e164a674d1
Source dataset
uspto-grants-2010_05
Patent number
US07718682B2

Reaction notes

Loading…