Sodium Iodide → 4-[3-Chloro-2-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-benzo[b]thiophen-6-yloxymethyl]-benzoic acid methyl ester

HRID 1173833Notes

Reaction equation

HRID 1173833 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].[Na+].[I-].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:33][O:34][C:35](=[O:44])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][CH:37]=1>CC(C)=O>[CH3:33][O:34][C:35](=[O:44])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42][O:24][C:21]2[CH:22]=[CH:23][C:3]3[C:2]([Cl:1])=[C:6]([CH2:7][CH:8]4[CH2:12][CH2:11][N:10]([CH:13]5[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]5)[C:9]4=[O:19])[S:5][C:4]=3[CH:20]=2)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 117103063-(3-Chloro-6-hydroxy-benzo[b]thiophen-2-ylmethyl)-1-cyclohexyl-pyrrolidin-2-one

Product 1

HCID 687712964-[3-Chloro-2-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-benzo[b]thiophen-6-yloxymethyl]-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Charge a vial with 3-(3-chloro-6-hydroxy-benzo[b]thiophen-2-ylmethyl)-1-cyclohexyl-pyrrolidin-2-one (175 mg, 0.481 mmol) and dissolve in acetone (0.3 M). Add NaI (72 mg, 0.481 mmol) and Cs2CO3 (1.25 g, 3.85 mmol) and stir at room temperature for 5 minutes. Add 4-bromomethyl-benzoic acid methyl ester (220 mg, 0.96 mmol) and heat to 50° C. overnight. Cool to room temperature, filter, concentrate, and purify over silica gel to afford 4-[3-chloro-2-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-benzo[b]thiophen-6-yloxymethyl]-benzoic acid methyl ester. Dissolve in ethanol (5 mL) and water (1 mL) and add potassium hydroxide (162 mg, 2.88 mmol) and heat to 50° C. overnight. Cool to room temperature filter and dry to afford the title compound (146 mg, 61%) as a white solid: Mass spectrum (apci) m/z=498.2 (M+H).

Workup

  1. filtrationfilter
  2. concentrationconcentrate
  3. custompurify over silica gel

Sources & evidence

ORD record
ord-f037b08614c44dcc8e9439a8cd19ca88
Source dataset
uspto-grants-2010_11
Patent number
US07834194B2

Reaction notes

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