Chloroacetonitrile → HCID 118062379, compound

HRID 920860Notes

Reaction equation

HRID 920860 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[CH2:29][C:30]#[N:31]>CN(C=O)C>[C:30]([CH2:29][N:10]1[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:12][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:9]1)#[N:31]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 42879153HCID 42879153, compound

Product 1

HCID 118062379HCID 118062379, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled solution of Intermediate 4B (7.0 g, 29.9 mmol) in DMF (45 mL), is added dropwise a solution of LHMDS (31.4 mL, 31.4 mmol, 1M in THF). The reaction mixture is allowed to stir for 5 min. and the ice bath is subsequently removed. 2-Chloroacetonitrile (2.482 g, 32.9 mmol) was added to the reaction mixture. The reaction was allowed to warm to RT and stir for 18 h. The reaction was quenched by the addition of 1.0 mL of a satd. aq. solution of NH4Cl. The reaction was diluted with equal parts water and EtOAc and the resulting mixture was allowed to stir vigorously for 15 min. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo. The crude reaction mixture was purified by silica gel chromatography (120 g REDISEP® column, eluting with a gradient from 0-40% EtOAc in hexanes). Fractions containing the product were combined and concentrated to afford Intermediate A131A (6.15 g, 75%) as a white solid. MS(ES) m/z=274 [M+H]+.

Workup

  1. customthe ice bath is subsequently removed
  2. stirringstir for 18 h
  3. customThe reaction was quenched by the addition of 1.0 mL of a satd
  4. additionThe reaction was diluted with equal parts water and EtOAc
  5. stirringto stir vigorously for 15 min
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe crude reaction mixture
  10. customwas purified by silica gel chromatography (120 g REDISEP® column
  11. washeluting with a gradient from 0-40% EtOAc in hexanes)
  12. additionFractions containing the product
  13. concentrationconcentrated
  14. customto afford Intermediate A131A (6.15 g, 75%) as a white solid

Sources & evidence

ORD record
ord-1b7ffbfb96da40d7941edf595d30a8f9
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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