Pyridinium, 1-fluoro-, 1,1,1-trifluoromethanesulfonate (1:1) → Methyl 2-(2-bromo-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetate

HRID 1952503Notes

Reaction equation

HRID 1952503 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:12]([C:14]2[CH:22]=[C:21]3[C:17]([CH:18]=[C:19]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[N:20]3[CH2:23][CH2:24][CH2:25][CH2:26][N:27]3[C:35](=[O:36])[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:28]3=[O:37])=[CH:16][CH:15]=2)=[O:13])=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH3:11])=[O:9].[O-]S(C(F)(F)[F:49])(=O)=O.F[N+]1C=CC=CC=1>C(Cl)Cl.CCOCC>[Br:1][C:2]1[S:3][C:4]([C:12]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([F:49])=[C:19]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:20]3[CH2:23][CH2:24][CH2:25][CH2:26][N:27]3[C:35](=[O:36])[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:28]3=[O:37])=[CH:16][CH:15]=2)=[O:13])=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH3:11])=[O:9]

Participants

5

Reactant 2

HCID 2724576Pyridinium, 1-fluoro-, 1,1,1-trifluoromethanesulfonate (1:1)HCID 67495985Methyl 2-(2-bromo-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-2-phenyl-1H-indole-6-carbonyl)-thiophene-3-yl)acetate

Product 1

HCID 67495279Methyl 2-(2-bromo-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetateYield 26.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5 (170 mg, 0.25 mmol) in 3 mL CH2Cl2 was added 1-fluoropyridinium triflate (75 mg, 0.30 mmol), and then the mixture was stirred at room temperature until no 5 was detected by NMR. The resulting mixture was diluted with 40 mL Et2O, washed with brine (2×10 mL), dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/9:1) gave 6 (45 mg, 26%) as a yellow amorphous solid. 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.78-7.63 (m, 6H), 7.56 (s, 1H), 7.50-7.41 (m, 5H), 4.25 (t, J=7.2 Hz, 2H), 3.71 (s, 3H), 3.69 (s, 2H), 3.49 (t, J=6.8 Hz, 2H), 1.66-1.60 (m, 2H), and 1.50-1.45 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 186.88, 170.13, 168.24, 143.76, 142.84, 140.39, 135.53, 134.70, 133.95, 133.90, 132.08, 132.02, 131.85, 131.39, 129.70, 128.91, 128.87, 128.72, 128.21, 128.18, 127.32, 127.12, 123.20, 121.58, 120.91, 119.94, 119.78, 116.78, 116.76, 112.32, 52.30, 43.37, 36.95, 34.81, 27.06, and 25.51.

Workup

  1. washwashed with brine (2×10 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customMPLC purification (Hex:EtOAc/9:1)

Sources & evidence

ORD record
ord-b8b44116ade0440aaebe569704e3989e
Source dataset
uspto-grants-2013_03
Patent number
US08404728B2

Reaction notes

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