Trifluoroacetic acid → Trifluoroacetic acid

HRID 71237Notes

Reaction equation

HRID 71237 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:15][CH2:16][C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:39]=[CH:38][C:25]([CH2:26][N:27]5[CH2:30][CH:29]([C:31]([O:33]C(C)(C)C)=[O:32])[CH2:28]5)=[CH:24][CH:23]=4)[N:18]=3)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43]>CO>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:15][CH2:16][C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:23]=[CH:24][C:25]([CH2:26][N:27]5[CH2:30][CH:29]([C:31]([OH:33])=[O:32])[CH2:28]5)=[CH:38][CH:39]=4)[N:18]=3)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[CH:5]=[CH:6][C:7]=1[F:8].[C:42]([OH:44])([C:41]([F:46])([F:45])[F:40])=[O:43]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66692530Tert-butyl 1-(4-(5-(2-(1-(3,4-difluorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Product 2

HCID 6422Trifluoroacetic acidYield 72%HCID 566439561-(4-(5-(2-(1-(3,4-Difluorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To tert-butyl 1-(4-(5-(2-(1-(3,4-difluorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (50.1 mg, 0.093 mmol) was added trifluoroacetic acid (2 mL, 26.0 mmol), and the mixture was stirred for 30 mins. The acid was evaporated off to give an oily residue. It was purified by preparative HPLC (Column: Phen-Luna 5u C18 21.2×100 mm, Sol A: 10% MeOH—90% H2O—0.1% TFA, Sol B: 90% MeOH—10% H2O—0.1% TFA, Start % B: 50, Final % B: 100, Gradient Time: 10 mins) to give pure 1-(4-(5-(2-(1-(3,4-difluorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid, TFA (40.5 mg, 0.067 mmol, 71.5% yield) as a foamy solid. LC/MS: m/e 482.14 (M+H)+. 1H NMR (400 MHz, CCl3D) δ ppm 12.51 (1H, br. s.), 8.02 (2H, d, J=7.03 Hz), 7.47 (2H, d, J=7.91 Hz), 6.98-7.21 (3H, m), 4.28-4.62 (4H, m), 4.01-4.24 (2H, m), 3.53-3.83 (1H, m), 2.49-2.68 (2H, m), 1.94-2.18 (4H, m), 1.21-1.72 (8H, m).

Workup

  1. customThe acid was evaporated off
  2. customto give an oily residue
  3. customIt was purified by preparative HPLC (Column

Sources & evidence

ORD record
ord-e9a5e9e5b7ac4dfdb3761e660a3077a0
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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