Hydrochloric Acid → (R)-5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid

HRID 927266Notes

Reaction equation

HRID 927266 reaction equation
O.[OH-].[Li+].[CH2:4]([N:11]1[C:20]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27]C)=[O:26])=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:29](=[O:40])[NH:30][C@@H:31]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[CH3:32])[CH:17]=2)[C:12]1=[O:41])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl>O.CO.C1COCC1>[CH2:4]([N:11]1[C:20]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:29](=[O:40])[NH:30][C@@H:31]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[CH3:32])[CH:17]=2)[C:12]1=[O:41])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 90093834(R)-methyl 5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

Product 1

HCID 90095415(R)-5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

Lithium hydroxide monohydrate (4.0 equiv.) in water (0.66 M) was added to a stirred mixture of (R)-methyl 5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (1 eq) in MeOH/THF (v/v=1/4) and the mixture was stirred at room temperature. After 2 h, the mixture was neutralized with 1 N HCl, extracted with EtOAc, dried over Na2SO4, filtered and evaporated to dryness. To the residue was added Et2O and sonicated, upon which some solid precipitated. The solids were filtered, triturated with Et2O and dried to yield (R)-5-(2-benzyl-6-((1-(4-fluorophenyl)ethyl)carbamoyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid. LCMS [M+H]+=501. 1H NMR (CDCl3, 500 MHz) δ ppm: 8.44 (d, 1H, J=8.5 Hz), 7.92 (br s, 1H), 7.71 (d, 1H, J=8.0 Hz), 7.40 (dd, 2H, J=5.0 Hz, J=8.5 Hz), 7.32-7.23 (m, 3H), 7.12 (d, 2H, J=7.5 Hz), 7.06 (t, 2H, J=9.0 Hz), 6.42 (s, 1H), 5.43 (br s, 2H), 5.39-5.35 (m, 1H), 2.63 (t, 2H, J=7.5 Hz), 2.37 (t, 2H, J=6.5 Hz), 1.70-1.64 (m, 4H), 1.63 (d, 3H, J=7.0 Hz).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. additionTo the residue was added Et2O
  6. customsonicated, upon which some solid
  7. customprecipitated
  8. filtrationThe solids were filtered
  9. customtriturated with Et2O
  10. customdried

Sources & evidence

ORD record
ord-c159f402e72748f7a512953b035e161e
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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