tert-Butyldimethylsilyl chloride → N-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-chloro-5,6-dimethyl-3-nitropyridin-4-amine

HRID 221595Notes

Reaction equation

HRID 221595 reaction equation
[Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([NH:11][C@@H:12]([CH3:15])[CH2:13][OH:14])[C:5]([CH3:16])=[C:4]([CH3:17])[N:3]=1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[Si:18]([O:14][CH2:13][C@@H:12]([NH:11][C:6]1[C:5]([CH3:16])=[C:4]([CH3:17])[N:3]=[C:2]([Cl:1])[C:7]=1[N+:8]([O-:10])=[O:9])[CH3:15])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

5

Reactant 2

HCID 28928tert-Butyldimethylsilyl chlorideHCID 86624127(2S)-2-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]propan-1-ol

Product 1

HCID 86624128N-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-chloro-5,6-dimethyl-3-nitropyridin-4-amineYield 92.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

(2S)-2-[(2-Chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]propan-1-ol (3.62 g, 13.9 mmol) was dissolved in 30 mL of dry pyridine under an atmosphere of N2. tert-Butyldimethylsilyl chloride (2.52 g, 16.7 mmol) and DMAP (0.17 g, 1.39 mmol) were added sequentially, and the reaction was heated to 50° C. and stirred overnight. The reaction mixture was then concentrated under reduced pressure. The resulting residue was partitioned between 50 mL of ethyl acetate and 50 mL of H2O. The layers were separated and the organic portion was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting material was passed through a plug of SiO2, eluting with a mixture of CH2Cl2, ethyl acetate and hexanes, to afford N-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-chloro-5,6-dimethyl-3-nitropyridin-4-amine (4.79 g) as an orange oil.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customThe resulting residue was partitioned between 50 mL of ethyl acetate and 50 mL of H2O
  3. customThe layers were separated
  4. washthe organic portion was washed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washeluting with a mixture of CH2Cl2, ethyl acetate and hexanes

Sources & evidence

ORD record
ord-3c2bd093ecc24bc6920bd2e8e8776e8a
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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