4-Toluenesulfonyl chloride → 6-fluoro-3-iodo-1-tosyl-1H-indole-5-carboxylic acid
Reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([I:11])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:12]([OH:14])=[O:13].[H-].[Na+].[S:17](Cl)([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([I:11])=[CH:7][N:8]2[S:17]([C:20]2[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=2)(=[O:19])=[O:18])=[CH:4][C:3]=1[C:12]([OH:14])=[O:13]Participants
Procedure
A solution of 6-fluoro-3-iodo-1H-indole-5-carboxylic acid (650 mg, 2.13 mmol) in DMF (5 mL) at 0° C. was treated with NaH (60% dispersion in mineral oil, 0.213 g, 5.33 mmol). After 30 minutes at 0° C., TsCl (0.447 g, 2.34 mmol) was added in 1 portion and the reaction mixture was warmed slowly in the ice bath (reached ca. 10° C.). After 1.5 h, the reaction mixture was poured onto ice, and the pH adjusted to pH 5 with 2 N HCl causing precipitation of the product. It was then collected by filtration, washing with water on a sintered glass frit, transferred to a flask and dried on a lyopholizer for 5 h affording 6-fluoro-3-iodo-1-tosyl-1H-indole-5-carboxylic acid (858 mg, 1.87 mmol, 88% yield) as an off-white amorphous solid. MS (ESI, pos. ion) m/z: 459.8 (M+H)+. The crude material was used in the subsequent step without further purification.
Workup
- waitAfter 1.5 h
- additionthe reaction mixture was poured onto ice
- customthe pH adjusted to pH 5 with 2 N HCl causing precipitation of the product
- filtrationIt was then collected by filtration
- washwashing with water on a sintered glass frit
- customtransferred to a flask
- customdried on a lyopholizer for 5 h
Sources & evidence
- ORD record
- ord-5c0d7eba67ae43b29bb0ce0b09f77ea9
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09321756B2
Reaction notes
Loading…