Dimethylformamide → HCID 68288666, compound

HRID 541231Notes

Reaction equation

HRID 541231 reaction equation
Br[C:2]1[N:7]=[CH:6][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)=[CH:4][CH:3]=1.[CH3:22][N:23](C=O)C>[C-]#N.[C-]#N.[Zn+2].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[N:7]=[CH:6][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)=[CH:4][CH:3]=1)#[N:23]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86672525HCID 86672525, compound2×

Product 1

HCID 68288666HCID 68288666, compoundYield 70%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a mixture of tert-butyl 4-(6-bromopyridin-3-yl)-4-hydroxypiperidine-1-carboxylate (compound 51.1, 1 g, 2.81 mmol, 1.00 equiv) in DMF (50 mL) under nitrogen at 50° C. was added Zn(CN)2 (400 mg, 3.42 mmol, 1.22 equiv) at 50° C. followed by Pd(PPh3)4 (200 mg, 0.17 mmol, 0.06 equiv) at 80° C. The resulting mixture was then stirred for 1 h at 120° C. After cooling to ambient temperature, the reaction was quenched by the addition of 200 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 1×200 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 (1:5-1:3) as eluent to yield 0.6 g (70%) of the title compound as a light yellow oil.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe reaction was quenched by the addition of 200 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 1×200 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-80cc65a2314244e3b4eaa1d9c031f426
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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