2-Bromopyridine → HCID 68313977, compound

HRID 2167040Notes

Reaction equation

HRID 2167040 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[C:13]([C:15](=[C:20]1[CH2:29][C:24]2([CH2:28][CH2:27][CH2:26][CH2:25]2)[O:23][CH2:22][CH2:21]1)[C:16]([O:18][CH3:19])=[O:17])#[N:14]>C1COCC1.[Cu](I)I>[C:13]([CH:15]([C:20]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:29][C:24]2([CH2:25][CH2:26][CH2:27][CH2:28]2)[O:23][CH2:22][CH2:21]1)[C:16]([O:18][CH3:19])=[O:17])#[N:14]

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 68313886Acetic acid, 2-cyano-2-(6-oxaspiro[4.5]dec-9-ylidene)-, methyl esterHCID 178418918HCID 178418918, compound

Product 1

HCID 68313977HCID 68313977, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-bromopyridine (14.4 ml, 150 mmo) in THF (75 ml) was added dropwise to a solution of isopropylmagnesium chloride (75 ml, 2M in THF) at 0° C. under N2, the mixture was then stirred at rt for 3 h, copper Iodide (2.59 g, 13.6 mmol) was added and allowed to stir at rt for another 30 min before a solution of a mixture of E and Z isomers of methyl 2-cyano-2-[6-oxaspiro[4.5]decan-9-ylidene]acetate (16 g, 150 mmol) in THF (60 ml) was added in 30 min. The mixture was then stirred at rt for 18 h. The reaction mixture was poured into a 200 g ice/2 N HCl (100 ml) mixture. The product was extracted with Et2O (3×300 ml), washed with brine (200 ml), dried (Na2SO4) and concentrated. The residual was purified by flash chromatography (100 g silica gel column, eluted by EtOAc in hexane: 3% 2 CV; 3-25%, 12 CV; 25-40% 6 CV gave methyl 2-cyano-2-[9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]acetate (15.44 g, 72% yield, m/z 315.0 [M+H]+ observed) as an amber oil.

Workup

  1. additionwas added in 30 min
  2. stirringThe mixture was then stirred at rt for 18 h
  3. extractionThe product was extracted with Et2O (3×300 ml)
  4. washwashed with brine (200 ml)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residual was purified by flash chromatography (100 g silica gel column
  8. washeluted by EtOAc in hexane

Sources & evidence

ORD record
ord-e3747d49a55a4bf4b972922fe2d1316f
Source dataset
uspto-grants-2015_06
Patent number
US09044469B2

Reaction notes

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