Acetate → 2-{3-[(2-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}ethyl)amino]phenyl}-3-furoic Acid

HRID 2234272Notes

Reaction equation

HRID 2234272 reaction equation
[OH-:1].[NH4+].[CH3:3][C:4]1[N:5]([C:9]2[CH:10]=[C:11]([C:15]3[O:16][CH:17]=[CH:18][C:19]=3[C:20]([O:22]CC)=[O:21])[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:7][N:8]=1.[C:25]([O-])(=O)[CH3:26].[ClH:29]>CO.C1(C)C=CC=CC=1.O>[Cl:29][C:10]1[CH:9]=[C:14]([C@@H:3]([OH:1])[CH2:4][NH:8][CH2:7][CH2:6][NH:5][C:9]2[CH:10]=[C:11]([C:15]3[O:16][CH:17]=[CH:18][C:19]=3[C:20]([OH:22])=[O:21])[CH:12]=[CH:13][CH:14]=2)[CH:13]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 175AcetateHCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 17952224ethyl 2-[3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]-3-furoate

Product 1

HCID 98011452-{3-[(2-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}ethyl)amino]phenyl}-3-furoic AcidYield 95%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Ammonium hydroxide (28%, 13 ml) was added over 10 min. to a mixture of ethyl 2-[3-(2-methyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]-3-furoate (13.0 g), deionized water (104 ml), and toluene (104 ml). After 30 min stirring, the organic layer was collected, washed with deionized water (26 ml), and concentrated to ca. 30 ml to remove traces of water azetropically. (R)-3-Chlorostyrene oxide (5.17 g) was added, and the resultant was heated under nitrogen at 110° C. for at least 14 h. The mixture was cooled to ca. 50° C. 1M Sodium hydroxide aqueous solution (77.8 ml) and methanol (39 ml) were added, and the apparatus was configured for distillation. After ca. 1 h, the homogeneous solution obtained was heated at reflux (ca. 4 h) until the hydrolysis was complete (HPLC acetate <2% @220 nm, a/a). The mixture was cooled to <50° C. Methanol (26 ml) and 1M hydrochloric acid (78 ml) were heated to ca. 50° C. The reaction mixture from above was added over 20 min, and the resultant slurry was cooled to <20° C. and aged for a further 30 min. The product was collected by filtration, washed with deionized water (2×26 ml), and dried in vacuo at 50° C. to yield 12.7 g (95%) of off-white solid.

Workup

  1. customthe organic layer was collected
  2. washwashed with deionized water (26 ml)
  3. concentrationconcentrated to ca. 30 ml
  4. customto remove traces of water azetropically
  5. addition(R)-3-Chlorostyrene oxide (5.17 g) was added
  6. temperatureThe mixture was cooled to ca. 50° C
  7. addition1M Sodium hydroxide aqueous solution (77.8 ml) and methanol (39 ml) were added
  8. distillationthe apparatus was configured for distillation
  9. waitAfter ca. 1 h
  10. customthe homogeneous solution obtained
  11. temperaturewas heated
  12. temperatureat reflux (ca. 4 h) until the hydrolysis
  13. temperatureThe mixture was cooled to <50° C
  14. additionThe reaction mixture from above was added over 20 min
  15. temperaturethe resultant slurry was cooled to <20° C.
  16. waitaged for a further 30 min
  17. filtrationThe product was collected by filtration
  18. washwashed with deionized water (2×26 ml)
  19. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-a103ece183a7411c898f434725daf12a
Source dataset
uspto-grants-2010_05
Patent number
US07709677B2

Reaction notes

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