Bromoacetonitrile → HCID 67130985, compound

HRID 1259836Notes

Reaction equation

HRID 1259836 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH2:4][C:5]1[C:6]([F:17])=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[C:12]([O:15][CH3:16])[CH:11]=[CH:10]2.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:30][C:31]#[N:32]>C1COCC1>[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:5]1[C:6]([F:17])=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[C:12]([O:15][CH3:16])[CH:11]=[CH:10]2)[CH2:30][C:31]#[N:32]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 67130870HCID 67130870, compound

Product 1

HCID 67130985HCID 67130985, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester (1.0 g, 4.0 mmol; prepared as in WO 2007/081597) in THF (10 mL) cooled to −78° C. was added LiHMDS (1M, 4.43 mL, 1.2 eq.) dropwise over 15 min. The resulting orange mixture was stirred at −78° C. for 2 h. Bromoacetonitrile (1.5 eq.) was added dropwise over 20 min and stirring was continued at −78° C. for an additional 2 h. The reaction was quenched with water and extracted with EA (3×). The combined org. phases were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by CC (Hept/EA 2:1 to 1:1) to afford the title intermediate as a colourless solid (953 mg, 82% yield). MS (ESI, m/z): 289.4 [M+H+].

Workup

  1. stirringstirring
  2. waitwas continued at −78° C. for an additional 2 h
  3. customThe reaction was quenched with water
  4. extractionextracted with EA (3×)
  5. washphases were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by CC (Hept/EA 2:1 to 1:1)

Sources & evidence

ORD record
ord-a8521b0db3b44f9ba28bd244c583f1ea
Source dataset
uspto-grants-2013_06
Patent number
US08466168B2

Reaction notes

Loading…