Potassium Carbonate → 5-Difluoromethoxy-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester

HRID 1930832Notes

Reaction equation

HRID 1930832 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([OH:17])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[C:25]([F:32])([F:31])C(OCC)=O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:17][CH:25]([F:32])[F:31])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 67843Acetic acid, 2-chloro-2,2-difluoro-, ethyl esterHCID 18630963tert-butyl 5-hydroxy-2,3-dihydro-1H-isoindole-2-carboxylate

Product 1

HCID 577532125-Difluoromethoxy-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture containing 0.68 mmol 5-Hydroxy-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (CAS: 226070-47-9), 0.68 mmol potassium carbonate and 0.68 mmol ethyl chlorodifluoroacetate in 1.5 ml DMF was stirred overnight at 65° C. The mixture was then partitioned between ethyl acetate and water and the organic phase was then separated, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluant: n-heptane/ethylacetate) to afford the title compound as a white solid (40% yield).

Workup

  1. customThe mixture was then partitioned between ethyl acetate and water
  2. customthe organic phase was then separated
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by chromatography on silica gel (eluant: n-heptane/ethylacetate)

Sources & evidence

ORD record
ord-aaae7a85e0d64aeba63a295ad6ae0875
Source dataset
uspto-grants-2012_05
Patent number
US08188139B2

Reaction notes

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