Anisole → 2-(3-Amino-2-oxo-6-phenyl-2H-pyridin-1-yl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxo-propyl)-acetamide

HRID 441189

Reaction equation

HRID 441189 reaction equation
C(OC([NH:11][C:12]1[C:13](=[O:38])[N:14]([CH2:24][C:25]([NH:27][CH:28]([CH:35]([CH3:37])[CH3:36])[C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])=[O:26])[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:16][CH:17]=1)=O)C1C=CC=CC=1.C1(OC)C=CC=CC=1.FC(F)(F)S(O)(=O)=O.C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C>[NH2:11][C:12]1[C:13](=[O:38])[N:14]([CH2:24][C:25]([NH:27][CH:28]([CH:35]([CH3:36])[CH3:37])[C:29](=[O:34])[C:30]([F:32])([F:33])[F:31])=[O:26])[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 7519AnisoleHCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 10369681{2-Oxo-6-phenyl-1-[(3,3,3-trifluoro-1-isopropyl-2-oxo-propylcarbamoyl)-methyl]-1,2-dihydro-pyridin-3-yl}-carbamic acid benzyl ester

Product 1

HCID 102500732-(3-Amino-2-oxo-6-phenyl-2H-pyridin-1-yl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxo-propyl)-acetamideYield 65%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3-benzyloxycarbonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (10 g) and anisole (6.6 g) in dichloromethane (100 mL) at 0° C. was added trifluoromethanesulphonic acid (9 mL, 15.3 g) while maintaining the temperature below 2° C. The reaction mixture was allowed to warm to room temperature in 30 min and kept at room temperature for a further 45 min before saturated aqueous sodium bicarbonate was added slowly to pH 7. Ethyl acetate was added, the phases separated and the aqueous phase extracted further with ethyl acetate. The combined organic extract was washed (brine), dried (MgSO4) and evaporated. The crude product was purified by trituration with hexane followed by trituration with diethyl ether to give the title product (which can be recrystallized from dichloromethane/hexane) as a white solid (4.85 g); TLC: Rf =0.40, ethyl acetate; 300 MHz NMR: 0.78-0.91 (m,6), 2.07-2.30 (m,1), 4.39 (d,1), 4.49 (d,1), 4.61 (t,1), 5.17 (s,1), 5.98 (d,1), 6.51 (d,1), 7.28-7.41 (m,5), 8.68 (d,1); MS: m/z=396(M+1).

Workup

  1. temperaturewhile maintaining the temperature below 2° C
  2. additionwas added slowly to pH 7
  3. customthe phases separated
  4. extractionthe aqueous phase extracted further with ethyl acetate
  5. extractionThe combined organic extract
  6. washwas washed (brine)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude product was purified by trituration with hexane

Sources & evidence

ORD record
ord-a786b00ddf114975b3966525e35cc5c5
Source dataset
uspto-grants-1996_05
Patent number
US05521179

Linked notes

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