Bromoacetonitrile → HCID 117992809, compound

HRID 922576Notes

Reaction equation

HRID 922576 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([CH:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:27]1COCC1.BrC[C:34]#[N:35]>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([CH3:27])([CH2:16][C:34]#[N:35])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 23714775LiHMDS tetrahydrofuranHCID 117992744HCID 117992744, compound

Product 1

HCID 117992809HCID 117992809, compoundYield 126.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The following reaction was repeated twice and combined to provide the yield below. To a −78° C. solution of crude ethyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate (69 g, 0.28 mol) in dry THF (1.0 L) was added lithium bis(trimethylsilyl)amide/THF (1.0 M, 400 mL, 0.40 mol) dropwise and stirred for 40 min. A solution of 2-bromoacetonitrile (54.5 g, 0.45 mol) in THF (70 mL) was then added dropwise over 1 h at −70° C. The reaction was then warmed to r.t. and stirred overnight. The reaction was quenched with saturated aqueous NH4CI and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated. Purification by silica gel column chromatography (2-8% EtOAc/PE) provided ethyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate (100 g, 62%) as an oil which solidified over several days. 1H NMR (600 MHz, CDCl3) δ 1.19 (t, 3H), 1.76 (s, 3H), 3.13 (q, 2H), 3.96 (s, 3H), 4.14-4.24 (m, 2H), 7.02 (d, 1H), 7.60 (d, 1H).

Workup

  1. customThe following reaction
  2. customto provide the
  3. customyield below
  4. stirringstirred overnight
  5. customThe reaction was quenched with saturated aqueous NH4CI
  6. extractionextracted with EtOAc
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by silica gel column chromatography (2-8% EtOAc/PE)

Sources & evidence

ORD record
ord-dc3d1dc21a60425283ec2849ca733bda
Source dataset
uspto-grants-2016_03
Patent number
US09278953B2

Reaction notes

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