Trifluoroacetic acid → HCID 57461728, compound

HRID 1896660Notes

Reaction equation

HRID 1896660 reaction equation
C(O)(C(F)(F)F)=O.[C:8]1([C:14]2[N:15]=[CH:16][N:17]([CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)[C:18]=2[C:19]2[CH:24]=[CH:23][N:22]=[CH:21][N:20]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>ClCCl>[C:8]1([C:14]2[N:15]=[CH:16][N:17]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:18]=2[C:19]2[CH:24]=[CH:23][N:22]=[CH:21][N:20]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58235125tert-Butyl 4-(4-phenyl-5-pyrimidin-4-yl-1H-imidazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 57461728HCID 57461728, compoundYield 52.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL) was added to a solution of tert-butyl 4-(4-phenyl-5-pyrimidin-4-yl-1H-imidazol-1-yl)piperidine-1-carboxylate (C22) (267 mg, 0.658 mmol) in dichloromethane (5 mL). After 2 hours, the reaction was concentrated in vacuo, and then treated with saturated aqueous sodium bicarbonate solution. The mixture was extracted with warm ethyl acetate, and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting light yellow oil solidified over the course of several days to provide 105 mg of product that was contaminated with approximately 20% of a related impurity. Fine white needles precipitated out of the aqueous layer; these were collected by filtration to provide additional product as a cream colored solid. Yield from aqueous layer: 54 mg, 0.18 mmol, 27%. 1H NMR (400 MHz, CDCl3) δ 1.83-1.93 (m, 2H), 2.12-2.18 (m, 2H), 2.72 (ddd, J=12.3, 12.3, 2.3 Hz, 2H), 3.20-3.25 (m, 2H), 4.85 (tt, J=12.0, 4.0 Hz, 1H), 7.19 (dd, J=5.3, 1.5 Hz, 1H), 7.30-7.36 (m, 3H), 7.42-7.45 (m, 2H), 7.85 (s, 1H), 8.54 (d, J=5.4 Hz, 1H), 9.30 (d, J=1.4 Hz, 1H).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. additiontreated with saturated aqueous sodium bicarbonate solution
  3. extractionThe mixture was extracted with warm ethyl acetate
  4. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customsolidified over the course of several days

Sources & evidence

ORD record
ord-7c1908d862544d979219277e54c67f8b
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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