Dimethylformamide → HCID 68288835, compound

HRID 541204Notes

Reaction equation

HRID 541204 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH3:22][N:23](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:22]([C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1)#[N:23]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68289059HCID 68289059, compound2×

Product 1

HCID 68288835HCID 68288835, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 4-(5-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate (compound 26.1, 1 g, 2.80 mmol, 1.00 equiv), zinc cyanide (400 mg, 3.42 mmol, 1.22 equiv), Pd(PPh3)4 (200 mg, 0.17 mmol, 0.06 equiv) in DMF (50 mL) was stirred under nitrogen for 2 h at 100° C. After cooling to room temperature, the reaction was then quenched by careful addition of 300 mL of FeSO4 (aq., sat.) and diluted with ethyl acetate. The resulting mixture was stirred vigorously then filtered through celite and washed with 1 M FeSO4, water, and ethyl acetate. The layers were separated and the aqueous phase was extracted with 2×100 mL of ethyl acetate. The combined organic layers were washed with 1×100 mL of brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:100-1:4) yield 0.5 g (58%) of the title compound as a yellow oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was then quenched by careful addition of 300 mL of FeSO4 (aq., sat.)
  3. additiondiluted with ethyl acetate
  4. stirringThe resulting mixture was stirred vigorously
  5. filtrationthen filtered through celite
  6. washwashed with 1 M FeSO4, water, and ethyl acetate
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with 2×100 mL of ethyl acetate
  9. washThe combined organic layers were washed with 1×100 mL of brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified

Sources & evidence

ORD record
ord-c4bd936b0e01449e8051ee9d2d18ef0a
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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