Trifluoroacetic acid → 5-(6-(5-(4-Fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid

HRID 927280Notes

Reaction equation

HRID 927280 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:49]=[CH:48][C:12]([CH2:13][C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[C:25](=[O:29])[N:24]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:23]([CH2:37][CH2:38][CH2:39][CH2:40][C:41]([O:43]C(C)(C)C)=[O:42])=[CH:22]4)[CH:15]=2)=[CH:11][CH:10]=1>ClCCl>[F:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[C:25](=[O:29])[N:24]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:23]([CH2:37][CH2:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[CH:22]4)[CH:15]=2)=[CH:48][CH:49]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90094533Tert-butyl 5-(6-(5-(4-fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

Product 1

HCID 736695375-(6-(5-(4-Fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acidYield 83.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL, 26.0 mmol) was added to a stirred, room temperature mixture of tert-butyl 5-(6-(5-(4-fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (100 mg, 0.175 mmol) in dichloromethane (2 mL) and the mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated to dryness and the residue was purified by column chromatography on silica gel, eluting with CH2Cl2/MeOH=10:1 to give 5-(6-(5-(4-fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid (75 mg, 0.146 mmol) as a yellow solid. LCMS [M+H]+=515. 1H NMR (500 MHz, CDCl3) δ ppm: 8.42 (d, J=8.51 Hz, 1H), 7.93 (d, J=1.26 Hz, 1H), 7.81 (d, J=1.58 Hz, 1H), 7.17-7.37 (m, 6H), 7.09 (t, J=8.51 Hz, 2H), 6.49 (s, 1H), 6.33 (s, 1H), 4.17 (s, 2H), 2.22-2.39 (m, 4H), 1.38-1.65 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue was purified by column chromatography on silica gel
  3. washeluting with CH2Cl2/MeOH=10:1

Sources & evidence

ORD record
ord-a762da80ee9d430890c41af05ffabaec
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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