Ethyl bromoacetate → HCID 58566448, compound

HRID 1909600Notes

Reaction equation

HRID 1909600 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1.Br[CH2:23][C:24]([O:26]CC)=[O:25].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH2:23][C:24]([OH:26])=[O:25])=[CH:19][CH:20]=2)[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 58566616HCID 58566616, compound

Product 1

HCID 58566448HCID 58566448, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 4-(2-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)ethyl)phenol (650) (164.1 mg, 0.573 mmol), ethyl bromoacetate (95.7 mg, 0.573 mmol), cesium carbonate (265 mg, 0.688 mmol) and acetonitrile (5 mL) was heated at 50° C. for 18 hours. The reaction was concentrated in vacuo and then purified by flash column chromatography with hexanes and EtOAc (30%). The ester was dissolved in tetrahydrofuran (1.0 mL), methanol (1.0 mL) and water (3 mL). Lithium hydroxide was added and the reaction was stirred at room temperature for 24 hours. The mixture was acidified with 1M HCl and diluted with EtOAc (3 mL). The organic layer was washed with brine (3 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield 2-(4-(2-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)ethyl)phenoxy)acetic acid (99). 1H NMR (400 MHz, CDCl3) δ 7.11 (d, J=7.8 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 6.69 (d, J=8.4 Hz, 1H), 6.56 (d, J=8.4 Hz, 1H), 4.65 (s, 2H), 2.96 (s, 2H), 2.88-2.73 (m, 4H), 1.43 (s, 6H). LC-MS ESI m/z: found 343.4 [M−H]−.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompurified by flash column chromatography with hexanes and EtOAc (30%)
  3. dissolutionThe ester was dissolved in tetrahydrofuran (1.0 mL)
  4. additionLithium hydroxide was added
  5. additiondiluted with EtOAc (3 mL)
  6. washThe organic layer was washed with brine (3 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-e7ec50f43a23480c84b02a562c3f35bc
Source dataset
uspto-grants-2013_12
Patent number
US08598374B2

Reaction notes

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