Toluene → 2-(3-Methyl-2-prop-2-ynyloxy-benzoylamino)-indan-2-carboxylic acid ethyl ester

HRID 1047829Notes

Reaction equation

HRID 1047829 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=2[OH:24])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:32](Br)[C:33]#[CH:34].C1(C)C=CC=CC=1>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=2[O:24][CH2:34][C:33]#[CH:32])[CH2:7][C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:14]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 1140TolueneHCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 593140982-(2-Hydroxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593141112-(3-Methyl-2-prop-2-ynyloxy-benzoylamino)-indan-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 100 mL round bottom flask containing the 2-(hydroxy-3-methyl-benzoyl)-indan-2-carboxylic acid ethyl ester (3) (0.29 g 0.855 mmol) is charged with DMF (4 mL) and a stirring bar is added. After dissolution of the starting material, K2SO4 (0.3 g, 2.17 mmol) is added followed by a solution of propargyl bromide in toluene (11.59 M, 240 μL, 2.78 mmol). After stirring for 62 h tlc analysis (silica, 1:1 EtOAc/heptanes) indicates that the starting material had been consumed. The material is cleanly converted to a UV positive spot with a slightly lower Rf. The reaction is diluted with EtOAc (80 mL) and filtered through a pad of Celite. The filtrate is transferred to a reparatory funnel. This is washed repeatedly with a saturated aqueous solution of NaHCO3 (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and evaporated in vacuo to yield 2.09 g of a light brown oil. This is purified (silica, 40 g ISCO column 10% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 50% EtOAc in heptanes for 10 column volumes). 17 mL fractions of UV positive eluent are collected. Fractions 4 through 10 are combined, evaporated in vacuo and pumped to constant weight to give 0.21 g of white solid.

Workup

  1. additionis added
  2. additionis added
  3. customhad been consumed
  4. additionThe reaction is diluted with EtOAc (80 mL)
  5. filtrationfiltered through a pad of Celite
  6. customThe filtrate is transferred to a reparatory funnel
  7. washThis is washed repeatedly with a saturated aqueous solution of NaHCO3 (2×50 mL) and brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-86cd92ca599c476f8f52babaa8215751
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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