Sodium Hydroxide → 4-[(1S)-1-[[(3R)-2-(2-phenoxyethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoic acid

HRID 2205308Notes

Reaction equation

HRID 2205308 reaction equation
[O:1]([CH2:8][CH2:9][N:10]1[C@@H:19]([C:20]([NH:22][C@H:23]([C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][CH:26]=2)[CH3:24])=[O:21])[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C1COCC1>[O:1]([CH2:8][CH2:9][N:10]1[C@@H:19]([C:20]([NH:22][C@H:23]([C:25]2[CH:26]=[CH:27][C:28]([C:29]([OH:31])=[O:30])=[CH:33][CH:34]=2)[CH3:24])=[O:21])[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 117706222methyl 4-[(1S)-1-[[(3R)-2-(2-phenoxyethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate

Product 1

HCID 862942384-[(1S)-1-[[(3R)-2-(2-phenoxyethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoic acidYield 64.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

Stir a mixture of methyl 4-[(1S)-1-[[(3R)-2-(2-phenoxyethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate (41.5 g, 90.5 mmol), THF (291 mL), and 2 M aqueous sodium hydroxide (181 mL, 360 mmol) at 40° C. overnight. Concentrate under reduced pressure to remove the THF. Add water (200 mL), then wash the aqueous layer with TBME (2×200 mL). Cool the aqueous layer to 5° C. and add concentrated aqueous hydrochloric acid with stirring until the pH reaches 2 (as estimated by pH paper analysis). With stirring, allow the mixture to warm to room temperature over 30 minutes, then isolate the solids by filtration. Add the solids to water (500 mL) and heat to 80° C. for one hour. Cool the mixture to room temperature, isolate the solids by filtration, and dry the solids in a vacuum oven at 45° C. overnight. Add the solids to isopropyl acetate (300 mL) and stir vigourously for 5 h. Isolate the solids by filtration, and dry the solids under reduced pressure to furnish the title compound as a white solid (26 g, 60% yield). Mass spectrum (m/z): 445 ([M+H]+).

Workup

  1. concentrationConcentrate under reduced pressure
  2. customto remove the THF
  3. washAdd water (200 mL), then wash the aqueous layer with TBME (2×200 mL)
  4. additionadd concentrated aqueous hydrochloric acid
  5. stirringwith stirring until the pH
  6. stirringWith stirring
  7. temperatureto warm to room temperature over 30 minutes
  8. customisolate the solids
  9. filtrationby filtration
  10. additionAdd the solids to water (500 mL)
  11. temperatureheat to 80° C. for one hour
  12. temperatureCool the mixture to room temperature
  13. customisolate the solids
  14. filtrationby filtration
  15. customdry the solids in a vacuum oven at 45° C. overnight
  16. additionAdd the solids to isopropyl acetate (300 mL)
  17. stirringstir vigourously for 5 h
  18. customIsolate the solids
  19. filtrationby filtration
  20. customdry the solids under reduced pressure

Sources & evidence

ORD record
ord-dd68f7be617c49cb94f74bbd89c20610
Source dataset
uspto-grants-2016_06
Patent number
US09371289B2

Reaction notes

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