Cesium carbonate → 2-(2-Cyclopropylmethoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

HRID 1047667Notes

Reaction equation

HRID 1047667 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.[Cs+].[Cs+].Br[CH2:33][CH:34]1[CH2:36][CH2:35]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][CH2:33][CH:34]2[CH2:36][CH2:35]2)[CH2:7][C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:14]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 593140982-(2-Hydroxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

Product 1

HCID 593142602-(2-Cyclopropylmethoxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl esterYield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 2-(2-hydroxy-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester (3) (400 mg, 1.18 mmol), anhydrous Cs2CO3 (769 mg, 2.36 mmol), and KI (40 mg, 0.24 mmol) in DMF (10 mL) is added bromomethylcyclopropane (229 μL, 2.36 mmol). The resulting reaction suspension is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (30 mL) and washed with water (1×5 mL) and brine (2×5 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (120 g silica gel, gradient elution: 10-40% EtOAc in heptane) to give a pure product (10) as white solid (330 mg, 71%).

Workup

  1. customThe resulting reaction suspension
  2. customAfter the removal of DMF in vacuo
  3. dissolutionthe residue is dissolved in EtOAc (30 mL)
  4. washwashed with water (1×5 mL) and brine (2×5 mL)
  5. dry with materialThe organic layer is dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography (120 g silica gel, gradient elution: 10-40% EtOAc in heptane)

Sources & evidence

ORD record
ord-9775557fc3d749859ce976c5d95b6197
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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