Methanol → HCID 86609347, compound

HRID 2108835Notes

Reaction equation

HRID 2108835 reaction equation
[CH3:1][NH:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:6]#[N:7].[BH4-].C1COCC1.CO.[C:22]([O:26][C:27](ON=C(C1C=CC=CC=1)C#N)=[O:28])([CH3:25])([CH3:24])[CH3:23]>O1CCOCC1>[CH3:1][NH:2][C:3]1[CH:4]=[C:5]([CH2:6][NH:7][C:27](=[O:28])[O:26][C:22]([CH3:25])([CH3:24])[CH3:23])[CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12]

Participants

6

Reactant 4

HCID 887MethanolHCID 938652-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrileHCID 1101939864910-48-1HCID 131727386borohydride THF

Product 1

HCID 86609347HCID 86609347, compoundYield 24.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

A 3-methylamino-4-nitrobenzonitrile (2.91 g, 16.4 mmol, Journal of Medicinal Chemistry (2001), 44(17), 2753-2771) was treated with borohydride-THF solution (1M THF solution, 65.6 ml) and the mixture was stirred for 3 hours at 0° C. After the addition of MeOH, the mixture was partitioned with water and EtOAc. The crude product was extracted with EtOAc and the organic layer was washed with water and dried over MgSO4. Then, filtration, evaporation gave the yellow colored oil, which was used for the next reaction without purification. The residue was dissolved in 1,4-dioxane (10 ml), and then 2[{(tert-butoxycarbonyl)oxy}imino]-2-phenylacetonitrile (3.13 g, 12.7 mmol) was added. After stirring for 14 hours at room temperature, the residue was concentrated in vacuo followed by the purification through silica gel column chromatography eluting with hexane/EtOAc (20:1) to give tert-butyl [(3-methylamino-4-nitrophenyl)methyl]carbamate as yellow colored solid (864 mg, 19%). 1H NMR (CDCl3): δ 1.47 (9H, s), 3.02 (3H, d, J=5.3 Hz), 4.31 (2H, d, J=5.9 Hz), 4.96 (1H, s), 6.56 (1H, d, J=9.3 Hz), 6.73 (1H, s), 8.08 (1H, brs), 8.14 (1H, d, J=8.6 Hz). MS (ESI) m/z 282 (M−H)+.

Workup

  1. customthe mixture was partitioned with water and EtOAc
  2. extractionThe crude product was extracted with EtOAc
  3. washthe organic layer was washed with water
  4. dry with materialdried over MgSO4
  5. filtrationThen, filtration, evaporation
  6. customgave the yellow colored oil, which
  7. customwas used for the next reaction without purification
  8. stirringAfter stirring for 14 hours at room temperature
  9. concentrationthe residue was concentrated in vacuo
  10. customfollowed by the purification through silica gel column chromatography
  11. washeluting with hexane/EtOAc (20:1)

Sources & evidence

ORD record
ord-84b221811a5a43e4909fc0131d688651
Source dataset
uspto-grants-2009_04
Patent number
US07514457B2

Reaction notes

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