Tetrahydrofuran → HCID 2960505, compound

HRID 484727Notes

Reaction equation

HRID 484727 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[Mg].O1CCCC1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)=[O:23])=[CH:18][CH:17]=1>CC(=O)C.C(=O)=O.C(O)(=O)C.CC1C=CC=CC=1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:22]([C:19]2[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=2)([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[OH:23])=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 99931-Bromo-4-fluorobenzeneHCID 5462224MagnesiumHCID 70230194-(4-Fluorobenzoyl)pyridine

Product 1

HCID 2960505HCID 2960505, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 18522661Acetone cardiceSolvent

Procedure

A Grignard-complex was previously prepared starting from 22.75 parts of 1-bromo-4-fluorobenzene, 3.2 parts of magnesium and 45 parts of anhydrous tetrahydrofuran. The whole was cooled in 2-propanone/CO2 to a temperature of -20° to -25° C. A solution of 20.1 parts of (4-fluorophenyl)(4-pyridinyl)methanone in 45 parts of anhydrous methylbenzene was added dropwise, during a 30 minutes-period, at -20° C. Upon completion, the whole was stirred overnight at room temperature. After cooling to 0° C., the reaction mixture was decomposed by the dropwise addition of 50 parts of acetic acid. After stirring for 1 hour at room temperature, the precipitated product was filtered off and set aside. From the filtrate, the organic layer was separated, washed with 50 parts of water, dried, filtered and evaporated. The solid residue and the precipitated product, which was set aside (see above), were washed with water and distilled azeotropically with 180 parts of methylbenzene. The solid distillate was suspended in 80 parts of acetonitrile. The product was filtered off and dried, yielding 28 parts (94%) of α,α-bis(4-fluorophenyl)-4-pyridinemethanol (intermediate 26).

Workup

  1. customA Grignard-complex was previously prepared
  2. customat -20° C
  3. temperatureAfter cooling to 0° C.
  4. stirringAfter stirring for 1 hour at room temperature
  5. filtrationthe precipitated product was filtered off
  6. customFrom the filtrate, the organic layer was separated
  7. washwashed with 50 parts of water
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. washwere washed with water
  12. distillationdistilled azeotropically with 180 parts of methylbenzene
  13. filtrationThe product was filtered off
  14. customdried

Sources & evidence

ORD record
ord-06b89bfc943a4c0fa4d2f941d656981a
Source dataset
uspto-grants-1985_08
Patent number
US04533665

Reaction notes

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