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

HRID 15978Notes

Reaction equation

HRID 15978 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 58374418HCID 58374418, compoundHCID 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-0d6a1cc7087a4efeb2c6c99318e08789
Source dataset
uspto-grants-2010_06
Patent number
US07732616B2

Reaction notes

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