Methyl iodide → HCID 66652839, compound

HRID 572554Notes

Reaction equation

HRID 572554 reaction equation
[C:1]([C:3]1[CH:21]=[CH:20][C:6]([CH2:7][NH:8][CH:9]([CH:17]([CH3:19])[CH3:18])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[C:5]([F:22])[CH:4]=1)#[N:2].[H-].[Na+].[CH3:25]I>CN(C=O)C>[C:1]([C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]([CH3:25])[CH:9]([CH:17]([CH3:18])[CH3:19])[C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])=[C:5]([F:22])[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66652808HCID 66652808, compound

Product 1

HCID 66652839HCID 66652839, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Tert-butyl 2-[(4-cyano-2-fluorobenzyl)amino]-3-methylbutanoate (7.2 g, 0.023 mol) in DMF (20 mL) was added dropwise to a stirred suspension of sodium hydride (2.2 g, 0.047 mol) in dry DMF (10 mL) at 00° C. The resulting mixture was stirred for 20 min at RT. Methyl iodide (6 mL, 0.094 mol) was then added dropwise at 0° C. and the mixture was allowed to stir for 3 hr at RT. The reaction mixture was quenched in ice water and extracted with ethyl acetate (250 mL). The organic layer was washed with water (3×100 mL) and dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography using petroleum ether and ethyl acetate as eluent, affording the title compound as colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.80 (d, J=10 Hz, 1H), 7.69 (d, J=7.9 Hz, 2H), 7.60 (t, J=7.4 Hz, 1H), 3.79 (d, J=15 Hz, 1H), 3.64 (d, J=15 Hz, 1H), 2.65 (d, J=10.7 Hz, 1H), 2.18 (s, 3H), 1.44 (s, 9H), 0.92-0.83 (m, 6H).

Workup

  1. stirringto stir for 3 hr at RT
  2. customThe reaction mixture was quenched in ice water
  3. extractionextracted with ethyl acetate (250 mL)
  4. washThe organic layer was washed with water (3×100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-4220775ed89747e9b4ce80cbd0b1098c
Source dataset
uspto-grants-2015_05
Patent number
US09029405B2

Reaction notes

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