Dichloromethane → HCID 59436570, compound

HRID 46324Notes

Reaction equation

HRID 46324 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[O:12][CH3:13].CC1(C)C(C)(C)OB([C:22]2[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH:27]=2)O1.C(=O)([O-])[O-].[K+].[K+].ClCCl>CN(C)C=O>[CH3:13][O:12][C:3]1[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=1[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH:23]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27570332-Bromo-1-methoxy-4-(trifluoromethyl)benzeneHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 59436570HCID 59436570, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 2-bromo-1-methoxy-4-(trifluoromethyl)benzene (825 mg, 3.23 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1.00 g, 3.23 mmol), potassium carbonate (1.34 g, 9.697 mmol) and [1,1-bis(diphenylphosphino)ferrocene]dichloro-palladium(11) complex with dichloromethane (1:1) (158 mg, 0.193 mmol) in N,N-dimethylformamide (19 mL) was purged with argon. After 30 minutes, the reaction mixture was heated at 90° C. and stirred for 22 hours before cooling to room temperature and filtering through Celite™, washing with ethyl acetate. The filtrate was concentrated in vacuo to ˜quarter and partitioned between water (100 mL) and ethyl acetate (75 mL). The aqueous layer was extracted with ethyl acetate (2×75 mL). Combined organic layers were washed with water, aqueous lithium chloride solution, saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by automated flash chromatography (24 g silica gel) eluting with hexanes:ethyl acetate (gradient 1:0 to 3:1, by volume) to afford the title compound as a clear oil, 1.1 g.

Workup

  1. customwas purged with argon
  2. temperaturebefore cooling to room temperature
  3. filtrationfiltering through Celite™
  4. washwashing with ethyl acetate
  5. concentrationThe filtrate was concentrated in vacuo to ˜quarter
  6. custompartitioned between water (100 mL) and ethyl acetate (75 mL)
  7. extractionThe aqueous layer was extracted with ethyl acetate (2×75 mL)
  8. washCombined organic layers were washed with water, aqueous lithium chloride solution, saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by automated flash chromatography (24 g silica gel)
  13. washeluting with hexanes

Sources & evidence

ORD record
ord-d52503135ae049d8a4966b83ac6db1b1
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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