Trifluoroacetic acid → HCID 131735434, compound

HRID 632526Notes

Reaction equation

HRID 632526 reaction equation
FC(F)(F)[C:3]([OH:5])=[O:4].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:22][C:23]1[C:24]([C:28]2[N:32]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([Br:40])[CH:34]=3)C(=O)O[N:29]=2)=[N:25][O:26][N:27]=1.[C:42]([O:46][C:47](=[O:52])[NH:48][CH2:49][CH:50]=O)([CH3:45])([CH3:44])[CH3:43]>C1COCC1>[Br:40][C:35]1[CH:34]=[C:33]([N:32]2[C:28]([C:24]3[C:23]([NH:22][CH2:50][CH2:49][NH:48][C:47](=[O:52])[O:46][C:42]([CH3:45])([CH3:44])[CH3:43])=[N:27][O:26][N:25]=3)=[N:29][C:3](=[O:4])[O:5]2)[CH:38]=[CH:37][C:36]=1[F:39]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 4247255tert-butyl N-(2-oxoethyl)carbamate2×HCID 5049666Sodium triacetoxyborohydrideHCID 591483883-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one

Product 1

HCID 131735434HCID 131735434, compoundYield 80.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

To a solution of trifluoroacetic acid (20.0 mL) and tetrahydrofuran (10.0 mL) was added sodium triacetoxyborohydride (10.59 g, 49.97 mmol, 10.0 equiv.) in portions with stirring under nitrogen. This mixture was stirred for 10 min at room temperature and then cooled to −5° C. A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (1.71 g, 5.0 mmol) and tert-butyl(2-oxoethyl)carbamate (Sigma-Aldrich) (1.99 g, 12.5 mmol, 2.5 equiv.) in THF (15.0 mL) was added drop-wise over 30 min with stirring while maintaining the temperature below 0° C. The reaction was stirred at −5 to 0° C. and additional portions of tert-butyl(2-oxoethyl)carbamate (0.20 g, 1.2 mmol, 0.24 equiv.) in THF (1.0 mL) were added drop-wise at 20 min, 40 min at 4 h intervals. HPLC indicated reaction completed after 5.25 h. The reaction mixture was poured into the ice-cold sodium bicarbonate (500 mL) and this solution was stirred at room temperature overnight. The precipitate was collected by filtration and washed with brine. The resulting residue was mixed with heptane (40 mL) and diethyl ether (40 mL) and stirred at room temperature for 5 h. The precipitate was collected by filtration, washed with diethyl ether and dried in a vacuum oven to give the desired product (1953 mg, 80.5%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.08 (m, 1H), 7.71 (m, 1H), 7.59 (t, 1H, J=8.7 Hz), 6.94 (m, 1H), 6.52 (m, 1H), 3.32 (m, 2H), 3.15 (m, 2H), 1.36 (s, 9H); C17H18BrFN6O5 (MW 485.26); LCMS (EI) m/e 507/509 (M++Na).

Workup

  1. stirringThis mixture was stirred for 10 min at room temperature
  2. stirringwith stirring
  3. temperaturewhile maintaining the temperature below 0° C
  4. stirringThe reaction was stirred at −5 to 0° C.
  5. customreaction
  6. waitcompleted after 5.25 h
  7. stirringthis solution was stirred at room temperature overnight
  8. filtrationThe precipitate was collected by filtration
  9. washwashed with brine
  10. additionThe resulting residue was mixed with heptane (40 mL) and diethyl ether (40 mL)
  11. stirringstirred at room temperature for 5 h
  12. filtrationThe precipitate was collected by filtration
  13. washwashed with diethyl ether
  14. customdried in a vacuum oven

Sources & evidence

ORD record
ord-8629742ebad749468ecc010698f9dce8
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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