Triethylamine → HCID 10458335, compound

HRID 1768470Notes

Reaction equation

HRID 1768470 reaction equation
[Si]([O:8][CH2:9][C:10]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:14]=[C:13]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])[CH2:12][N:11]1[C:23]([N:25]([CH3:32])[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:24])(C(C)(C)C)(C)C.FC(F)(F)S(O[CH2:45][CH:46]([F:48])[F:47])(=O)=O.C(N(CC)CC)C>C1COCC1>[F:48][CH:46]([F:47])[CH2:45][N:29]1[CH2:30][CH2:31][CH:26]([N:25]([CH3:32])[C:23]([N:11]2[CH2:12][C:13]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=3[F:22])=[CH:14][C:10]2([CH2:9][OH:8])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:24])[CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 10098834HCID 10098834, compound

Product 1

HCID 10458335HCID 10458335, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To 87 mg (0.16 mmol) of amine 7-2 in THF in a sealed tube was added 41 mg (0.19 mmol) of 2,2-difluoroethyl trifluoromethane sulfonate and 67 μL (0.48 mmol) of triethylamine. After stirring 2.5 h at 70° C., the mixture was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with brine, dried over MgSO4, and concentrated by rotary evaporation. The residue was dissolved in 5 mL CH2Cl2 and 1 mL of trifluroacetic acid was added. After stirring for 30 min at room temperature, the solvents were removed by rotary evaporation, the residue was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with brine, dried over MgSO4, and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with MeOH/CHCl3 to provide 10-1 as a white solid. Data for 10-1: 1HNMR (500 MHz, CDCl3) δ 7.7-7.3 (m, 5H), 7.1-6.9 (m, 3H), 6.3 (s, 1H), 5.8 (m, 1H), 5.4 (m, 1H), 4.8 (m, 1H), 4.6 (m, 1H), 4.4 (m, 1H), 4.0 (m, 1H), 3.7 (m, 1H), 3.0 (m, 2H), 2.9 (s, 3H), 2.75 (m, 2H), 2.3 (m, 2H), 1.9 (m, 2H), 1.6 (m, 1H) ppm. HRMS (ES) calc'd M+H for C26H29F4N3O2: 492.2269. Found: 492.2250.

Workup

  1. customthe mixture was partitioned between EtOAc and saturated NaHCO3
  2. customthe layers were separated
  3. washthe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated by rotary evaporation
  6. dissolutionThe residue was dissolved in 5 mL CH2Cl2
  7. addition1 mL of trifluroacetic acid was added
  8. stirringAfter stirring for 30 min at room temperature
  9. customthe solvents were removed by rotary evaporation
  10. customthe residue was partitioned between EtOAc and saturated NaHCO3
  11. customthe layers were separated
  12. washthe organic phase was washed with brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated by rotary evaporation
  15. customThe residue was purified by column chromatography on silica gel with MeOH/CHCl3

Sources & evidence

ORD record
ord-b88d2132d3194825aec7e3a673efc173
Source dataset
uspto-grants-2007_06
Patent number
US07235580B2

Reaction notes

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