Imidazole → 5-[3-(tert-Butyl-dimethyl-silanoxy)-propyl]-2'-trifluoromethyl-biphenyl-3,4-diamine

HRID 1518130Notes

Reaction equation

HRID 1518130 reaction equation
[NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:18])([F:17])[F:16])=[CH:4][C:3]=1[CH2:19][CH2:20][CH2:21][OH:22].N1C=CN=C1.[CH3:28][C:29]([Si:32](Cl)([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C(Cl)Cl>[C:29]([Si:32]([CH3:34])([CH3:33])[O:22][CH2:21][CH2:20][CH2:19][C:3]1[C:2]([NH2:1])=[C:7]([NH2:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:16])([F:17])[F:18])[CH:4]=1)([CH3:31])([CH3:30])[CH3:28]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 592800973-(4,5-Diamino-2'-trifluoromethyl-biphenyl-3-yl)-propan-1-ol

Product 1

HCID 592801095-[3-(tert-Butyl-dimethyl-silanoxy)-propyl]-2'-trifluoromethyl-biphenyl-3,4-diamineYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(4,5-Diamino-2′-trifluoromethyl-biphenyl-3-yl)-propan-1-ol (101 mg, 0.324 mmol, as prepared in the previous step) was placed in an 8 mL vial equipped with a magnetic stir bar, and DCM (2 mL) was added via pipette. Imidazole (1.1 eq., 24.5 mg, 0.356 mmol) and TBSCl (1.1 eq., 53.7 mg, 0.356 mmol) were added sequentially as solids, and the reaction was stirred at RT for 2 h. The reaction was filtered, the precipitate was washed once with DCM (5 mL), and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography on a 24-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 1:1, v/v over 30 min, yielding 93.2 mg (68%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 7.69 (d, J=7.8 Hz, 1H), 7.49 (t, J=7.5 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H), 7.32 (d, J=7.6 Hz, 1H), 6.61 (s, 1H), 6.59 (s, 1H), 3.66 (t, J=5.9 Hz, 2H), 3.52 (br. s., 4H), 2.65 (t, J=7.3 Hz, 2H), 1.75-1.87 (m, 2H), 0.91 (s, 9H), 0.07 (s, 6H).

Workup

  1. customvial equipped with a magnetic stir bar
  2. filtrationThe reaction was filtered
  3. washthe precipitate was washed once with DCM (5 mL)
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe crude product was purified by column chromatography on a 24-g SiO2 pre-packed column
  6. washeluting with EtOAc/hexanes, 0:1 to 1:1, v/v over 30 min

Sources & evidence

ORD record
ord-06051f999f904a6694f8ed025ea663b4
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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