2-Bromo-1,4-difluorobenzene → HCID 118590599, compound

HRID 1054440Notes

Reaction equation

HRID 1054440 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[F:9].C([Mg]Cl)(C)C.[O:15]=[C:16]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23]>C1COCC1>[F:9][C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[C:16]1([OH:15])[CH2:21][CH2:20][CH2:19][CH2:18][N:17]1[C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23]

Participants

5

Reactant 3

HCID 678622-Bromo-1,4-difluorobenzeneHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 118590599HCID 118590599, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-bromo-1,4-difluorobenzene (5.15 g, 25.9 mmol) in dry THF (77 ml, 15 v) at −78° C. was added i-PrMgCl (2M, 19.5 ml, 38.8 mmol) drop wise and stirred for 1 h at room temperature then cooled again to −78° C. and added tert-butyl 2-oxopiperidine-1-carboxylate (dissolved in dry THF) (6.0 g, 31.0 mmol) drop wise and reaction mixture was stirred for 2 h at room temperature. After completion of reaction, quenched with sat.NH4Cl solution and diluted with ethyl acetate. Organic layer was separated and water layer was extracted with ethyl acetate. Combined organic layer were washed with water, brine and dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude Int-17 (9.4 g) which was directly used for the next step.

Workup

  1. temperaturethen cooled again to −78° C.
  2. customreaction mixture
  3. stirringwas stirred for 2 h at room temperature
  4. customAfter completion of reaction
  5. customquenched
  6. additionNH4Cl solution and diluted with ethyl acetate
  7. customOrganic layer was separated
  8. extractionwater layer was extracted with ethyl acetate
  9. washCombined organic layer were washed with water, brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customto afford crude Int-17 (9.4 g) which

Sources & evidence

ORD record
ord-9e077f5e976b460d9cca96711427ec96
Source dataset
uspto-grants-2016_07
Patent number
US09394305B2

Reaction notes

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