4-Toluenesulfonyl chloride → 6-Fluoro-1-tosylindoline

HRID 56068

Reaction equation

HRID 56068 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][C:13]1[CH:21]=[C:20]2[C:16]([CH2:17][CH2:18][NH:19]2)=[CH:15][CH:14]=1.[NH4+].[Cl-]>C1COCC1.N1C=CC=CC=1>[F:12][C:13]1[CH:21]=[C:20]2[C:16]([CH2:17][CH2:18][N:19]2[S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 25517Ammonium ChlorideHCID 2604006-fluoro-2,3-dihydro-1H-indole

Product 1

HCID 606033976-Fluoro-1-tosylindolineYield 61.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Toluenesulfonyl chloride (460 mg, 2.4 mmol) was slowly added to a solution of 6-fluoro-2,3-dihydro-1H-indole (220 mg, 1.6 mmol) in THF (6 mL) and pyridine (260 μL). The reaction mixture was stirred at room temperature overnight. Upon the completion of the reaction, the mixture was cooled to 0° C., neutralized with aq. sat. NH4Cl (10 mL) and extracted with EtOAc (3×10 mL). The combined extracts were sequentially washed with aq. sat. NH4Cl (3×10 mL), brine (10 mL) and dried (MgSO4). The crude product was concentrated and dried over high vacuum. Chromatography of the residue (EtOAc/hexanes=1/3) gave 283 mg (0.98 mmol) of the title product. Yield: 61%, colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.67 (d, J=8.2 Hz, 2H), 7.35 (dd, J=10.0, 2.3 Hz, 1H), 7.23 (d, J=8.2 Hz, 2H), 6.97 (m, 1H), 6.62 (m, 1H), 3.90 (t, J=8.4 Hz, 2H), 2.84 (t, J=8.4 Hz, 2H), 2.35 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3): δ 162.5 (d, J=241.4 Hz), 144.5, 143.3 (d, J=11.7 Hz), 133.6, 129.8, 127.2, 127.0 (d, J=2.6 Hz), 125.7 (d, J=9.8 Hz), 110.0 (d, J=22.6 Hz), 102.8 (d, J=28.4 Hz), 50.7, 27.1, 21.5 ppm.

Workup

  1. customUpon the completion of the reaction
  2. temperaturethe mixture was cooled to 0° C.
  3. extractionextracted with EtOAc (3×10 mL)
  4. washThe combined extracts were sequentially washed with aq. sat. NH4Cl (3×10 mL), brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationThe crude product was concentrated
  7. customdried over high vacuum

Sources & evidence

ORD record
ord-3bbb81c43f5643c897226bdd9bb9b9fe
Source dataset
uspto-grants-2016_09
Patent number
US09434699B2

Linked notes

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