Imidazole → 4-Chloro-2-trifluoroacetyl-6-(tert-butyldimethylsilyloxy)aniline

HRID 2298528Notes

Reaction equation

HRID 2298528 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([Cl:9])=[CH:4][C:3]=1[C:10](=[O:15])[C:11]([F:14])([F:13])[F:12].N1C=CN=C1.FC(F)(F)S(O[Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])(=O)=O>CN(C=O)C>[NH2:1][C:2]1[C:7]([O:8][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])=[CH:6][C:5]([Cl:9])=[CH:4][C:3]=1[C:10](=[O:15])[C:11]([F:14])([F:12])[F:13]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 159230922'-Amino-5'-chloro-3'-hydroxy-2,2,2-trifluoroacetophenone

Product 1

HCID 159230934-Chloro-2-trifluoroacetyl-6-(tert-butyldimethylsilyloxy)aniline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred, cooled (0° C.) solution of 29.3 g (122 mmol) of 2′-amino-5′-chloro-3′-hydroxy-2,2,2-trifluoroacetophenone in 280 mL of DMF was added 23.8 g (350 mmol) of imidazole followed by 66 g (250 nmol) of t-butyldimethylsilyl trifluoromethanesulfonate over 10 min. The reaction was stirred 5 h at 0° C. and diluted with 800 mL of 1:1 ether-hexanes. The solution was washed twice with water and once with brine, dried (MgSO4) and concentrated under reduced pressure to give a dark oil. The crude product was rapidly passed through an 800 g plug of silica gel (elution with hexanes followed by 6:1 hexanes-ether) to afford, after evaporation of solvent, 42.5 g (98%) of 2′-amino-5′-chloro-3′-(t-butyldimethylsilyloxy)-2,2,2-trifluoroacetophenone as a yellow oil. The product solidified after extended evacuation at 0.01 torr to give a yellow solid, mp 45-46.5° C. 1H NMR (300 MHz, CDCl3) δ7.34-7.36(m, 1H); 6.85(d, 1H, J=2.2 Hz); 6.7-6.8(br. s, 2H); 1.03(s, 9H); 0.30(s, 6H). High resolution mass spec: calculated for C14H20NO2ClF3Si(M+H)+: 354.0904, found: 354.0900. Analysis calculated for C14H19NO2ClF3Si: C, 47.52; H, 5.41; N, 3.97; Cl, 10.02. Found: C, 47.71; H, 5.36; N, 3.87; Cl, 10.02.

Workup

  1. washThe solution was washed twice with water and once with brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customto give a dark oil
  5. customto afford
  6. customafter evaporation of solvent, 42.5 g (98%) of 2′-amino-5′-chloro-3′-(t-butyldimethylsilyloxy)-2,2,2-trifluoroacetophenone as a yellow oil
  7. customto give a yellow solid, mp 45-46.5° C

Sources & evidence

ORD record
ord-5d30632276984ca684e1780a1ca64e69
Source dataset
uspto-grants-2002_12
Patent number
US06492515B2

Reaction notes

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