Hydrochloric Acid → Trifluoroacetic acid

HRID 1506502Notes

Reaction equation

HRID 1506502 reaction equation
C1(C(=[N:14][CH:15]([CH2:21][CH2:22][C:23]2[CH:24]=[C:25]3[C:48](=[CH:49][CH:50]=2)[C:29]2=[N:30][O:31][C:32]([C:33]4[C:37]([C:38]([F:41])([F:40])[F:39])=[C:36]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[O:35][N:34]=4)=[C:28]2[CH2:27][CH2:26]3)[C:16]([O:18]CC)=[O:17])C2C=CC=CC=2)C=CC=CC=1.Cl.[OH-].[Na+].[C:54]([OH:60])([C:56]([F:59])([F:58])[F:57])=[O:55]>C(OCC)C.CO.O>[NH2:14][CH:15]([CH2:21][CH2:22][C:23]1[CH:24]=[C:25]2[C:48](=[CH:49][CH:50]=1)[C:29]1=[N:30][O:31][C:32]([C:33]3[C:37]([C:38]([F:39])([F:40])[F:41])=[C:36]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[O:35][N:34]=3)=[C:28]1[CH2:27][CH2:26]2)[C:16]([OH:18])=[O:17].[C:54]([OH:60])([C:56]([F:59])([F:58])[F:57])=[O:55]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 86669931Ethyl 2-(diphenylmethyleneamino)-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate

Product 2

HCID 6422Trifluoroacetic acidYield 30.6%HCID 671708432-Amino-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To a stirred solution of ethyl 2-(diphenylmethyleneamino)-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 91A, 34 mg, 0.050 mmol) and water (0.025 mL) in diethyl ether (1.5 mL) was added 6 N aqueous HCl (50 μL, 0.300 mmol). The mixture was stirred at room temperature for 30 min. The ether layer was removed and the residue was mixed with MeOH (0.5 mL) and 2 N aqueous sodium hydroxide (0.5 mL, 1.000 mmol). After being stirred at room temperature for 30 min, the mixture was acidified with TFA to get a clear solution. 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-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid, TFA (10 mg, 0.015 mmol, 30.6% yield) as a white solid. The compound had an HPLC retention time=3.40 min. (condition C); LC/MS M+1=484.1; 1H NMR (400 MHz, MeOD) δ ppm 7.91 (1H, d, J=7.7 Hz), 7.78 (2H, d, J=8.1 Hz), 7.59-7.72 (3H, m), 7.33 (1H, s), 7.30 (1H, dd, J=8.0, 1.7 Hz), 4.00 (1H, t, J=6.3 Hz), 3.04-3.10 (4H, m), 2.74-2.95 (2H, m), 2.12-2.36 (2H, m).

Workup

  1. customThe ether layer was removed
  2. stirringAfter being stirred at room temperature for 30 min
  3. customto get a clear solution
  4. customPurification
  5. 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-787a32f877f34c9d9468897acc463898
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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