Water → Trifluoroacetic acid

HRID 1506506Notes

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[C:24]([C:25]([F:28])([F:27])[F:26])=[C:23]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[O:22][N:21]=3)=[C:15]1[CH2:14][CH2:13]2)[C:3]([O:5]CC)=[O:4].[OH-:39].[Na+].[OH2:41]>CO>[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[C:24]([C:25]([F:26])([F:28])[F:27])=[C:23]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[O:22][N:21]=3)=[C:15]1[CH2:14][CH2:13]2)[C:3]([OH:5])=[O:4].[C:24]([OH:41])([C:25]([F:28])([F:27])[F:26])=[O:39]

Participants

Conditions

Temperature: 66 °C

Procedure

A mixture of ethyl 2-amino-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 94A, isomer 1, 8 mg, 0.015 mmol), 2 M aqueous solution of sodium hydroxide (0.015 mL, 0.030 mmol), water (0.1 mL) and methanol (0.2 mL) was stirred at 66° C. under nitrogen for 30 min. 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 2-amino-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid, TFA (6 mg, 9.42 μmol, 61.9% yield) as a white solid. The compound had an HPLC retention time=3.45 min. (condition C); LC/MS M+1=498.5.

Workup

customPurification
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-0e4e86187cac4854b4b67023535d83ab
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216972B2

Reaction notes

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