Trifluoroacetic acid → HCID 57640346, compound

HRID 2111896Notes

Reaction equation

HRID 2111896 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:15][C:16]2[N:17]=[CH:18][S:19][CH:20]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[CH2:21]([N:14]([CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)[CH2:15][C:16]1[N:17]=[CH:18][S:19][CH:20]=1)[CH:22]([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 68577252HCID 68577252, compound

Product 1

HCID 57640346HCID 57640346, compoundYield 99.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled (0° C.) solution of 4-{isobutyl-[(thiazol-4-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (540 mg, 1.53 mmol, 1 eq.) in anhydrous dichloromethane (3 ml), is added anisole (2.5 g, 23 mmol, 15 eq.) and trifluoroacetic acid (2.6 g, 23 mmol, 15 eq.). The reaction is allowed to warm to room temperature and stirred for 4-5 hours. The reaction mixture is loaded on a SCX-2 column. The column is first washed with methanol and then the base eluted with 20% 2N NH3 in methanol in dichloromethane. The solvents are removed in vacuo to afford isobutyl-(piperidin-4-yl)-[(thiazol-4-yl)methyl]-amine (387 mg). m/z=254 (M+1); 1H NMR (CDCl3): δ=8.27 (1H, d), 7.22-7.21 (1H, m), 3.86 (2H, d), 3.15 (2H, brd), 2.62-2.49 (3H, m), 2.30 (2H, d), 2.03 (1H, brs), 1.78 (2H, d), 1.66-1.59 (1H, m), 1.50-1.40 (2H, m), 0.86 (6H, d).

Workup

  1. washThe column is first washed with methanol
  2. washthe base eluted with 20% 2N NH3 in methanol in dichloromethane
  3. customThe solvents are removed in vacuo

Sources & evidence

ORD record
ord-63104efa18884c45b6f85e9dab1929ce
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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