HCID 57995586, compound → 2-(4-Amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester

HRID 1183617Notes

Reaction equation

HRID 1183617 reaction equation
[CH:1]1([CH2:4][O:5][C:6](=[O:26])[CH:7]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[C:14]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1>CC(O)=O.O.[Zn]>[CH:1]1([CH2:4][O:5][C:6](=[O:26])[CH:7]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1

Participants

5

Reactant 1

HCID 57995586HCID 57995586, compound

Product 1

HCID 579955632-(4-Amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl esterYield 75%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

2-(3-Cyclopropylmethoxy-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (34.0 g, 94.2 mmol) was dissolved in AcOH (300 mL) and water (20 mL). Then, Zn powder (60.0 g, 923 mmol) was added in portions. The reaction mixture was refluxed for 1 h and after cooling the precipitate was filtered. The solvent was evaporated and water (150 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL) and the combined organic phases were washed with water (3×100 mL) and brine (100 mL). Drying of the organic phase was performed with magnesium sulfate. The evaporation of the solvent gave crude product as a brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc to give 2-(4-amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (23 g, 75%). 1H NMR (300 MHz, CDCl3/TMS): δ 6.73-6.61 (m, 3H), 3.94-3.78 (m, 6H), 3.53 (t, J=7.7 Hz, 1H), 1.94-1.85 (m, 1H), 1.65-1.56 (m, 1H), 1.52-1.43 (m, 1H), 1.28-1.18 (m, 1H), 1.11-1.03 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.64-0.58 (m, 2H), 0.53-0.47 (m, 2H), 0.36-0.33 (m, 2H), 0.24-0.21 (m, 2H); 13C NMR (75 MHz, CDCl3/TMS): δ 174.6, 146.4, 135.3, 129.3, 120.5, 114.6, 111.2, 73.1, 69.0, 49.2, 42.7, 25.8, 22.6, 22.4, 10.4, 9.8, 3.2.

Workup

  1. temperatureThe reaction mixture was refluxed for 1 h
  2. temperatureafter cooling the precipitate
  3. filtrationwas filtered
  4. customThe solvent was evaporated
  5. additionwater (150 mL) was added
  6. extractionThe reaction mixture was extracted with EtOAc (3×100 mL)
  7. washthe combined organic phases were washed with water (3×100 mL) and brine (100 mL)
  8. customDrying of the organic phase
  9. customThe evaporation of the solvent
  10. customgave crude product as a brown oil, which
  11. customwas purified by silica gel gradient column chromatography by use of Heptane-EtOAc

Sources & evidence

ORD record
ord-5de9f46ff0934ddf87f352629fba3ef1
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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