Ethyl bromoacetate → ethyl 2-(3-cyano-2,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

HRID 1189555Notes

Reaction equation

HRID 1189555 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[S:17]([N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)(=[O:19])=[O:18])=[C:5]([CH3:9])[C:6]=1[C:7]#[N:8].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.C(OCC)(=O)C>[C:7]([C:6]1[C:5]([CH3:9])=[C:4]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[S:17]([N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)(=[O:19])=[O:18])[N:3]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:2]=1[CH3:1])#[N:8]

Participants

7

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 583109832,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole-3-carbonitrile

Product 1

HCID 58310969ethyl 2-(3-cyano-2,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetateYield 44.7%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole-3-carbonitrile (513.6 mg, 1.495 mmol), TBAI (55.2 mg, 0.150 mmol), cesium carbonate (1462 mg, 4.49 mmol), and ethyl bromoacetate (250 μl, 2.243 mmol) in DMF (7.5 ml) was heated at 60° C. for 4 hours. The mixture was diluted in ethyl acetate (100 ml) and washed with water (50 ml×3). The organic layer was dried, filtered, and evaporated to give an oil. This oil was purified by column chromatography (0 to 40% ethyl acetate in hexanes) to give ethyl 2-(3-cyano-2,4-dimethyl-5-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (286.9 mg, 0.668 mmol, 44.7% yield). 1H NMR (CDCl3/400 MHz) δ (ppm) 7.92-7.88 (m, 1H), 7.44-7.38 (m, 1H), 7.35-7.29 (m, 1H), 6.96-6.92 (m, 1H), 4.36 (s, 2H), 4.28 (s, 2H), 3.94 (q, 2H), 3.38-3.30 (m, 4H), 2.27 (s, 3H), 2.13 (s, 3H), 1.98-1.92 (m, 4H), 1.11 (t, 3H). MS m/z: 430.3 (M+1).

Workup

  1. washwashed with water (50 ml×3)
  2. customThe organic layer was dried
  3. filtrationfiltered
  4. customevaporated
  5. customto give an oil
  6. customThis oil was purified by column chromatography (0 to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3378e88baa064e45874072963c8313e3
Source dataset
uspto-grants-2014_03
Patent number
US08674115B2

Reaction notes

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