4-(Bromomethyl)-1-fluoro-2-phenoxybenzene → 1-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1-buten-3-ol

HRID 1596825Notes

Reaction equation

HRID 1596825 reaction equation
C([Li])CCC.[O:6]([C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[F:21])[CH2:16]Br)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Cl:22][C:23]1[CH:36]=[CH:35][C:26]([C:27]([CH:32]2[CH2:34][CH2:33]2)=[C:28]([F:31])[CH:29]=[O:30])=[CH:25][CH:24]=1>O1CCCC1>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:27]([CH:32]2[CH2:34][CH2:33]2)=[C:28]([F:31])[CH:29]([OH:30])[CH2:16][C:15]2[CH:18]=[CH:19][C:20]([F:21])=[C:13]([O:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:14]=2)=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 129227144-(Bromomethyl)-1-fluoro-2-phenoxybenzeneHCID 540115002-Fluoro-3-cyclopropyl-3-(p-chlorophenyl)acrylaldehydeHCID 178418339Butyllithium2×

Product 1

HCID 541714401-(p-Chlorophenyl)-1-cyclopropyl-2-fluoro-4-(4-fluoro-3-phenoxyphenyl)-1-buten-3-olYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of lithium n-butyltellurolate (10.5 mmol, n-BuTeLi), generated in situ from n-butyllithium (4.2 mL of 2.5 M solution in hexane, 10.5 mmol) and Te powder (1.34 g, 10.5 mmol) in tetrahydrofuran (10 mL) at 0° C., is treated with a solution of 3-phenoxy-4-fluorobenzyl bromide (2.81 g, 10 mmol) in tetrahydrofuran (10 mL) at 0° C., stirred for 30 minutes, cooled to −78° C., treated with a solution of n-butyllithium (4.2 mL of 2.5 M solution in hexane, 10.5 mmol), stirred for 30 minutes at −78° C., treated with a solution of p-chloro-β-cyclopropyl-α-fluorocinnamaldehyde (2.24 g, 10 mmol) in tetrahydrofuran (5 mL), warmed to room temperature with stirring for 3 hours, quenched with 2 N hydrochloric acid, and extracted with ethyl acetate. The combined organic extracts are washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a residue. Flash chromatography of the residue on silica gel using a 1:4 ethyl acetate/hexanes solution gives the title product (3.5 g, 82% yield) which is identified by NMR spectral analyses.

Workup

  1. stirringstirred for 30 minutes at −78° C.
  2. temperaturewarmed to room temperature
  3. stirringwith stirring for 3 hours
  4. customquenched with 2 N hydrochloric acid
  5. extractionextracted with ethyl acetate
  6. washThe combined organic extracts are washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto obtain a residue

Sources & evidence

ORD record
ord-68c2816718c8432cab6e1261a07ed3f8
Source dataset
uspto-grants-2001_09
Patent number
US06291721B1

Reaction notes

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