Trifluoroacetic acid → 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide

HRID 1050143Notes

Reaction equation

HRID 1050143 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][C:32]([CH3:43])([CH3:42])[CH2:33][O:34][Si](C(C)(C)C)(C)C)=[C:27]([C:44]([F:47])([F:46])[F:45])[CH:26]=3)=[O:23])=[CH:17][C:16]=2[F:48])=[C:11]([O:49][CH2:50][CH3:51])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][C:32]([CH3:43])([CH3:42])[CH2:33][OH:34])=[C:27]([C:44]([F:45])([F:47])[F:46])[CH:26]=3)=[O:23])=[CH:17][C:16]=2[F:48])=[C:11]([O:49][CH2:50][CH3:51])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 904228192-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 904232742-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamideYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a mixture of 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (4.5 g, 4.83 mmol) in DCM (30 mL) was added TFA (4.46 mL, 57.9 mmol). The mixture was stirred at 25° C. for 2 h. Then the reaction residue was concentrated, added to MeCN (50 mL), made basic with NH4OH and concentrated. The crude material was purified by silica column chromatography (PE/EA=1:1). All fractions found to contain product by TLC (PE/EA=1:1, Rf=0.6) were combined and concentrated to yield a light yellow solid of 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (4.2 g, 4.19 mmol, 87% yield): 1H NMR (400 MHz, CD3OD) δ 7.97 (s, 1H), 7.88 (s, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.51-7.43 (m, 3H), 7.38 (t, J=7.2 Hz, 2H), 7.35-7.29 (m, 2H), 7.26-7.16 (m, 2H), 6.50 (s, 1H), 5.38 (s, 2H), 4.14-4.11 (m, 2H), 3.77 (s, 2H), 2.80 (s, 2H), 2.03 (s, 2H), 1.32 (t, J=6.8 Hz, 3H), 0.86 (s, 6H); ES-LCMS m/z 611.2 (M+H).

Workup

  1. concentrationThen the reaction residue was concentrated
  2. additionadded to MeCN (50 mL)
  3. concentrationconcentrated
  4. customThe crude material was purified by silica column chromatography (PE/EA=1:1)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c52be412514a453792c9790b2e9279b4
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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