Sodium Iodide → 4-[3-Chloro-2-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-benzo[b]thiophen-6-yloxy]-butyric acid tert-butyl ester
Reaction equation
[Cl:1][C:2]1[C:3]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:4]=2[S:5][C:6]=1[CH2:7][CH:8]1[CH2:12][CH2:11][N:10]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:9]1=[O:19].[C:25]([O:29][C:30](=[O:35])[CH2:31][CH2:32][CH2:33]Br)([CH3:28])([CH3:27])[CH3:26].[I-].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>>[C:25]([O:29][C:30](=[O:35])[CH2:31][CH2:32][CH2:33][O:24][C:21]1[CH:22]=[CH:23][C:3]2[C:2]([Cl:1])=[C:6]([CH2:7][CH:8]3[CH2:12][CH2:11][N:10]([CH:13]4[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]4)[C:9]3=[O:19])[S:5][C:4]=2[CH:20]=1)([CH3:28])([CH3:27])[CH3:26]Participants
Reactant 4
Product 1
Procedure
Using the procedure to synthesize Example 12 and using reagents 3-(3-chloro-6-hydroxy-benzo[b]thiophen-2-ylmethyl)-1-cyclohexyl-pyrrolidin-2-one (175 mg, 0.481 mmol), 4-bromo-butyric acid tert-butyl ester (215 mg, 0.962 mmol), sodium iodide (72 mg, 0.481 mmol), and cesium carbonate (1.25 g, 3.85 mmol) afford crude 4-[3-chloro-2-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-benzo[b]thiophen-6-yloxy]-butyric acid tert-butyl ester. Dissolve ester in trifluoroacetic acid (25 mL) and stir for 1.5 hr. Evaporate and dissolve in 1M NaOH and wash with ether. Bring aqueous layer to a pH of ˜2 with 6M HCl, filter, and dry. Purified on silica gel (30-50% ethyl acetate in hexanes) to give the title compound (105 mg, 49%) as a tan solid: Mass spectrum (apci) m/z=450.1 (M+H).
Workup
- customto synthesize Example 12
Sources & evidence
- ORD record
- ord-db52f89b968240e796321905535ffa0c
- Source dataset
- uspto-grants-2010_11
- Patent number
- US07834194B2
Reaction notes
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