Lithium Hexamethyldisilazide → (S)-2-(4-Bromo-2-fluorophenylamino)-N-(2-(tert-butyldimethylsilyloxy)propoxy)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide

HRID 422827Notes

Reaction equation

HRID 422827 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:20])[C:11](=[O:19])[CH:12]=[CH:13][C:14]=2[C:15]([O:17]C)=O)=[C:4]([F:21])[CH:3]=1.[Si:22]([O:29][C@@H:30]([CH3:34])[CH2:31][O:32][NH2:33])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:20])[C:11](=[O:19])[CH:12]=[CH:13][C:14]=2[C:15]([NH:33][O:32][CH2:31][C@@H:30]([O:29][Si:22]([C:25]([CH3:26])([CH3:28])[CH3:27])([CH3:24])[CH3:23])[CH3:34])=[O:17])=[C:4]([F:21])[CH:3]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 58374418(S)-O-(2-((tert-Butyldimethylsilyl)oxy)propyl)hydroxylamineHCID 66673525Methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Product 1

HCID 86612533(S)-2-(4-Bromo-2-fluorophenylamino)-N-(2-(tert-butyldimethylsilyloxy)propoxy)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.050 g, 0.14 mmol) and (S)—O-(2-(tert-butyldimethylsilyloxy)propyl)hydroxylamine (0.072 g, 0.35 mmol) in THF (1.50 mL) at 0° C. was slowly added lithium bis(trimethylsilyl)amide (0.70 ml, 0.70 mmol). After addition, the reaction mixture was stirred for 1 hour at room temperature and then quenched by with saturated NaHCO3. The reaction mixture was partitioned between EtOAc and sat NaCl. The layers were separated and the aqueous layer was back-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure to yield a crude brown solid that was used without further purification in the next step.

Workup

  1. customat 0° C.
  2. additionAfter addition
  3. customquenched by with saturated NaHCO3
  4. customThe reaction mixture was partitioned between EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous layer was back-extracted with EtOAc (1×)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto yield a crude brown solid that
  11. customwas used without further purification in the next step

Sources & evidence

ORD record
ord-b8c48c3579774890b4ee9d4299466d48
Source dataset
uspto-grants-2012_01
Patent number
US08101639B2

Reaction notes

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