Hydrochloric Acid → HCID 11259662, compound

HRID 1270992Notes

Reaction equation

HRID 1270992 reaction equation
O(C1C=CC(NC(=O)N[C@@H](CC2C=CC=CC=2)/C=C/C(O)=O)=CC=1)C1C=CC=CC=1.[N:31]1([CH2:36][CH2:37][NH:38][C:39](=[O:68])/[CH:40]=[CH:41]/[C@@H:42]([NH:50][C:51]([NH:53][C:54]2[CH:59]=[CH:58][C:57]([O:60][C:61]3[CH:66]=[CH:65][C:64](F)=[CH:63][CH:62]=3)=[CH:56][CH:55]=2)=[O:52])[CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)CCC[CH2:32]1.Cl.O(C1C=CC(N=C=O)=CC=1)C1C=CC=CC=1>C(Cl)Cl.O1CCOCC1.C1COCC1>[CH3:32][NH:31][CH2:36][CH2:37][NH:38][C:39](=[O:68])/[CH:40]=[CH:41]/[C@@H:42]([NH:50][C:51]([NH:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[CH:56][CH:55]=1)=[O:52])[CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 27348964-Phenoxyphenyl isocyanateHCID 11386775HCID 11386775, compoundHCID 69430499HCID 69430499, compound

Product 1

HCID 11259662HCID 11259662, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

(E)-(S)-4-[3-(4-Phenoxy-phenyl)-ureido]-5-phenyl-pent-2-enoic acid. To a solution of (E)-(S)-4-tert-butoxycarbonylamino-5-phenyl-pent-2-enoic acid (Example 11, step A) (2.12 g, 7.26 mmol) in CH2Cl2 (73 mL) was added 4 M HCl in 1,4-dioxane (25 mL), and the resulting solution was stirred at rt for 15 min. The solvent was removed. To a solution of the resulting residue and TEA (0.74 g, 7.26 mmol) in THF (73 mL) cooled to 0° C., was added 4-phenoxy phenyl isocyanate (1.53 g, 7.26 mmol), and the mixture was stirred for 30 min. The solution was brought to rt and was stirred for an additional 3 h. The solvent was removed, and the resulting yellow oil was purified by column chromatography on silica gel using a gradient of 0–35% (MeOH (10% acetic acid)/CH2Cl2). The purified product was recrystallized from CH2Cl2 and was washed with hexanes to afford 1.45 g (50%) of the desired product as a grey solid. Rf=0.47 (5% MeOH (1% NH4OH)/CH2Cl2). MS (electrospray): mass calculated for C24H22N2O4, 402.16; m/z found, 403.1 [M+H]+, 425.1 [M+Na]+, 827.3 [2M+Na]+. 1H NMR (400 MHz, DMSO-d6): 12.34 (br s, 1H), 8.51 (s, 1H), 7.40–7.20 (m, 9H), 7.08–7.05 (m, 1H), 6.93–6.91 (m, 4H), 6.86 (d, J=5.0 Hz, 1H), 6.35 (d, J=8.5 Hz, 1H), 5.77 (dd, J=15.6, 1.6 Hz, 1H), 4.70–4.61 (m, 1H), 2.93 (dd, J=13.7, 6.1 Hz, 1H), 2.84 (dd, J=13.7, 7.9 Hz, 1H).

Workup

  1. customThe solvent was removed
  2. stirringthe mixture was stirred for 30 min
  3. customwas brought to rt
  4. stirringwas stirred for an additional 3 h
  5. customThe solvent was removed
  6. customthe resulting yellow oil was purified by column chromatography on silica gel using a gradient of 0–35% (MeOH (10% acetic acid)/CH2Cl2)
  7. customThe purified product was recrystallized from CH2Cl2
  8. washwas washed with hexanes

Sources & evidence

ORD record
ord-43d41aea960e4591b36657d0b03d15cf
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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