Ethyl Acetate → 5-Amino-4-fluoro-2-(1-methylcyclohexyl)phenyl methyl carbonate

HRID 404597Notes

Reaction equation

HRID 404597 reaction equation
[C:1](=[O:22])([O:20][CH3:21])[O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-])=O)[C:6]([F:12])=[CH:5][C:4]=1[C:13]1([CH3:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.C([O-])=O.[NH4+].C(OCC)(=O)C>CO.[Pd]>[C:1](=[O:22])([O:20][CH3:21])[O:2][C:3]1[CH:8]=[C:7]([NH2:9])[C:6]([F:12])=[CH:5][C:4]=1[C:13]1([CH3:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 2723923Ammonium formateHCID 593950134-Fluoro-2-(1-methylcyclohexyl)-5-nitrophenyl methyl carbonate

Product 1

HCID 513584455-Amino-4-fluoro-2-(1-methylcyclohexyl)phenyl methyl carbonateYield 82.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 4-fluoro-2-(1-methylcyclohexyl)-5-nitrophenyl methyl carbonate 24.1 g, 77.5 mmol) in 220 mL of CH3OH was added Pd/C 10%, 9.6 g, then ammonium formate (26.7 g, 445 mmol) was portion-wise added to the above reaction mixture at room temperature until starting material is consumed. The mixture was filtrated and the filtrate was evaporated under vacuum. The residue was purified by column chromatography on silica gel diluted with hexane:ethyl acetate=50:1 to give 5-amino-4-fluoro-2-(1-methylcyclohexyl)phenyl methyl carbonate as a red brown oil (17.9 g, 82% yield). 1H NMR (400 MHz, CDCl3) δ 6.99 (d, J=13.6 Hz, 1H), 6.51 (d, J=8.4 Hz, 1H), 3.89 (s, 3H), 3.43 (brs, 2H), 1.96-1.91 (m, 2H), 1.58-1.38 (m, 8H), 1.18 (s, 3H): MS m/z: 281.9 [M+H]+

Workup

  1. additionadded to the above reaction mixture at room temperature
  2. customis consumed
  3. filtrationThe mixture was filtrated
  4. customthe filtrate was evaporated under vacuum
  5. customThe residue was purified by column chromatography on silica gel
  6. additiondiluted with hexane

Sources & evidence

ORD record
ord-8cc2c97891064c8ca8cbf2c93af942a4
Source dataset
uspto-grants-2014_06
Patent number
US08748612B2

Reaction notes

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