Lithium Hydroxide → 2-{4-[(2R)-2-({(3S)-2-[(tert-Butyl)oxycarbonyl](3-1,2,3,4-tetrahydroisoquinolyl)}carbonylamino)-3-(4-chlorophenyl)propanoyl]piperazinyl}benzoic acid

HRID 228077Notes

Reaction equation

HRID 228077 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18]([NH:20][C@H:21]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=2)[C:22]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=3[C:32]([O:34]C)=[O:33])[CH2:26][CH2:25]2)=[O:23])=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-]>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18]([NH:20][C@H:21]([CH2:40][C:41]2[CH:42]=[CH:43][C:44]([Cl:47])=[CH:45][CH:46]=2)[C:22]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=3[C:32]([OH:34])=[O:33])[CH2:26][CH2:25]2)=[O:23])=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 58714303methyl 2-{4-[(2R)-2-({(3S)-2-[(tert-butyl)oxycarbonyl](3-1,2,3,4-tetrahydroisoquinolyl)}carbonylamino)-3-(4-chlorophenyl)propanoyl]piperazinyl}benzoate

Product 1

HCID 587143202-{4-[(2R)-2-({(3S)-2-[(tert-Butyl)oxycarbonyl](3-1,2,3,4-tetrahydroisoquinolyl)}carbonylamino)-3-(4-chlorophenyl)propanoyl]piperazinyl}benzoic acidYield 61.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a 150 mL round-bottomed flask equipped with magnetic stirring was added methyl 2-{4-[(2R)-2-({(3S)-2-[(tert-butyl)oxycarbonyl](3-1,2,3,4-tetrahydroisoquinolyl)}carbonylamino)-3-(4-chlorophenyl)propanoyl]piperazinyl}benzoate (1.6 g, 2.4 mmol) in THF (30 mL). A soln of LiOH (Aldrich) (303 mg, 7.14 mmol) in H2O (ca. 10 mL) was added and the reaction was heated at 60° C. for 12 h. After cooling to RT, the mixture was concentrated in vacuo and diluted with EtOAc (100 mL). A 10% soln of citric acid (25 mL) was added, the organic layer was separated, and the aqueous layer was extracted with EtOAc (2×25 mL). The organic layers were combined, washed with H2O, and brine, dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound as a white solid (960 mg). MS (ESI, pos. ion) m/z: 647 (M+H). Calc'd for C35H39ClN4O6: 646.26.

Workup

  1. customTo a 150 mL round-bottomed flask equipped
  2. temperatureAfter cooling to RT
  3. concentrationthe mixture was concentrated in vacuo
  4. additiondiluted with EtOAc (100 mL)
  5. additionA 10% soln of citric acid (25 mL) was added
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  8. washwashed with H2O, and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-32fda53da3f84fee873fa8560be9a019
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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