Acetic Acid → N2-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-2,3-pyridinediamine

HRID 420686Notes

Reaction equation

HRID 420686 reaction equation
[CH3:1][C:2]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@@H:8]([NH:18][C:19]1[C:24]([N+:25]([O-])=O)=[CH:23][CH:22]=[C:21]([O:28][CH3:29])[N:20]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])[CH3:3].C(O)(=O)C>CO.[Zn]>[CH3:4][C:2]([Si:5]([CH3:30])([CH3:31])[O:6][CH2:7][C@@H:8]([NH:18][C:19]1[C:24]([NH2:25])=[CH:23][CH:22]=[C:21]([O:28][CH3:29])[N:20]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:1])[CH3:3]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 58001750N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamine

Product 1

HCID 58001755N2-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-2,3-pyridinediamineYield 80%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of N-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-3-nitro-2-pyridinamine (642.6 g, 1.436 mol) in MeOH (12 L) was added a suspension of zinc dust (938 g, 14.35 mol) in MeOH (4 L). Acetic acid (411 ml, 7.18 mol) was added dropwise over ˜30 min such that the temperature remained below 36° C. When the addition was complete the mixture was stirred for 15 min. The reaction mixture was filtered through celite and the cake was washed with EtOAc (8 L). The mixture was washed with brine (8 L) and the layers were separated. The aqueous phase was extracted with EtOAc (8+6 L) then the organic phases were combined, washed with saturated NaHCO3 (8 L), brine (8 L), dried over MgSO4 (1 kg) and filtered. The filtrate was evaporated to give 478 g (80%) of N2-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-2,3-pyridinediamine as a dark red viscous oil.

Workup

  1. customremained below 36° C
  2. additionWhen the addition
  3. filtrationThe reaction mixture was filtered through celite
  4. washthe cake was washed with EtOAc (8 L)
  5. washThe mixture was washed with brine (8 L)
  6. customthe layers were separated
  7. extractionThe aqueous phase was extracted with EtOAc (8+6 L)
  8. washwashed with saturated NaHCO3 (8 L), brine (8 L)
  9. dry with materialdried over MgSO4 (1 kg)
  10. filtrationfiltered
  11. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-3c6041743185418f90a5058c7e6ac1c9
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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