Imidazole → N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamine

HRID 420685Notes

Reaction equation

HRID 420685 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([NH:9][C@@H:10]([CH2:13][O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][OH:12])[C:6]([N+:22]([O-:24])=[O:23])=[CH:5][CH:4]=1.Cl[Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27].N1C=CN=C1>CN(C=O)C>[CH3:30][C:29]([Si:26]([CH3:28])([CH3:27])[O:12][CH2:11][C@@H:10]([NH:9][C:7]1[C:6]([N+:22]([O-:24])=[O:23])=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[N:8]=1)[CH2:13][O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 58001740(2R)-2-{[6-(methyloxy)-3-nitro-2-pyridinyl]amino}-3-[(phenylmethyl)oxy]-1-propanol

Product 1

HCID 58001750N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamineYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R)-2-{[6-(methyloxy)-3-nitro-2-pyridinyl]amino}-3-[(phenylmethyl)oxy]-1-propanol (675.8 g) in DMF (2.37 L) was added chloro(1,1-dimethylethyl)dimethylsilane (382.0 g) in portions. Then, imidazole (331.2 g) was added in portions and the mixture was stirred at room temperature for 1.5 h. The reaction mixture was evaporated and the resulting orange gum was partitioned between EtOAc (3 L) and H2O (3 L). The layers were separated and the aqueous was extracted with EtOAc (2.5+2 L). The organic layers were combined, dried over MgSO4 (˜500 g), filtered and evaporated to give an orange oil. The crude product was purified by column chromatography (10 kg silica, 9:1 heptane:EtOAc) to give N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamine (774.7 g, 100%) as a bright yellow solid.

Workup

  1. customThe reaction mixture was evaporated
  2. customthe resulting orange gum was partitioned between EtOAc (3 L) and H2O (3 L)
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with EtOAc (2.5+2 L)
  5. dry with materialdried over MgSO4 (˜500 g)
  6. filtrationfiltered
  7. customevaporated
  8. customto give an orange oil
  9. customThe crude product was purified by column chromatography (10 kg silica, 9:1 heptane:EtOAc)

Sources & evidence

ORD record
ord-5410bbbd438e4f9dad6a2e440fe5a172
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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