Methanol → Trifluoroacetic acid

HRID 1506404Notes

Reaction equation

HRID 1506404 reaction equation
[NH2:1][C:2]([CH3:38])([CH2:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:35](=[CH:36][CH:37]=1)[C:16]1=[N:17][O:18][C:19]([C:20]3[CH:21]=[N:22][N:23]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:24]=3[C:25]([F:28])([F:27])[F:26])=[C:15]1[CH2:14][CH2:13]2)[C:3]([O:5]CC)=[O:4].[OH-:39].[Na+].[CH3:41][OH:42]>>[NH2:1][C@@:2]([CH3:38])([CH2:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:35](=[CH:36][CH:37]=1)[C:16]1=[N:17][O:18][C:19]([C:20]3[CH:21]=[N:22][N:23]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:24]=3[C:25]([F:26])([F:28])[F:27])=[C:15]1[CH2:14][CH2:13]2)[C:3]([OH:5])=[O:4].[C:41]([OH:42])([C:25]([F:28])([F:27])[F:26])=[O:39]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 67170053ethyl 2-amino-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate

Product 2

HCID 6422Trifluoroacetic acidYield 63.1%HCID 67171874(2S)-2-amino-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid

Procedure

A solution of ethyl 2-amino-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 50D, 4 mg, 7.63 μmol) and 10% aqueous sodium hydroxide (0.2 mL) in methanol (0.2 mL) was stirred under nitrogen at 60° C. for 1.5 hr and then room temperature overnight. Purification using reverse phase HPLC (PHENOMENEX® Luna Axia 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, and lyophilization gave (2S)-2-amino-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid, TFA (3 mg, 4.82 μmol, 63.1% yield) as a white solid. The compound had an HPLC retention time=3.07 min (condition C); LC/MS M+1=497.3; 1H NMR (400 MHz, MeOD) δ ppm 8.14 (1H, s), 7.86 (1H, d, J=7.7 Hz), 7.54-7.64 (5H, m), 7.22-7.30 (2H, m), 3.03 (2H, t, J=7.0 Hz), 2.90 (2H, t, J=7.0 Hz), 2.83 (1H, td, J=13.1, 5.0 Hz), 2.65 (1H, td, J=13.0, 5.0 Hz), 2.26 (1H, td, J=13.5, 4.7 Hz), 2.10 (1H, td, J=13.5, 4.7 Hz), 1.62 (3H, s).

Workup

  1. customroom temperature overnight
  2. customPurification
  3. concentrationphase HPLC (PHENOMENEX® Luna Axia 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, and lyophilization

Sources & evidence

ORD record
ord-077882a33e674f0bb5c6a4cbb1cdade2
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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