2-(5-Cyclopropylmethoxy-2-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester → 2-(5-Cyclopropylmethoxy-2-fluoro-4-amino-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester

HRID 1512378Notes

Reaction equation

HRID 1512378 reaction equation
[CH:1]1([CH2:4][O:5][C:6](=[O:27])[CH:7]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][CH:20]3[CH2:22][CH2:21]3)[C:15]([N+:23]([O-])=O)=[CH:14][C:13]=2[F:26])[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1>CCO.[Pd]>[CH:1]1([CH2:4][O:5][C:6](=[O:27])[CH:7]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][CH:20]3[CH2:21][CH2:22]3)[C:15]([NH2:23])=[CH:14][C:13]=2[F:26])[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:2][CH2:3]1

Participants

4

Reactant 1

HCID 687350142-(5-Cyclopropylmethoxy-2-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester

Product 1

HCID 579955732-(5-Cyclopropylmethoxy-2-fluoro-4-amino-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

2-(5-cyclopropylmethoxy-2-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (10.0 g, 26.4 mmol) was dissolved in EtOH (200 mL) and hydrogenated at 50 psi, 25° C. for 24 h over 10% Pd—C (1 g). The mixture was filtered and the solvent evaporated to give crude a brown oil, which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 6.7 g, (72%) of 2-(5-cyclopropylmethoxy-2-fluoro-4-amino-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ 6.73 (d, J=6.9 Hz, 1H), 6.40 (d, J=11.0 Hz, 1H), 4.00-3.70 (m, 5H), 1.91-1.81 (m, 1H), 1.65-1.56 (m, 1H), 1.51-1.39 (m, 1H), 1.28-1.18 (m, 1H), 1.12-1.00 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.63-0.57 (m, 2H), 0.53-047 (m, 2H), 0.35-0.28 (m, 2H), 0.25-0.18 (m, 2H); 13C NMR (75 MHz, CDCl3/TMS): δ 174.2, 154.8 (d, 1JCF=236.0 Hz), 142.6, 136.6 (d, 3JCF=11.5 Hz), 114.1 (d, 2JCF=16.8 Hz), 111.6 (d, 3JCF=4.8 Hz), 101.6 (d, 2JCF=28.2 Hz), 73.8, 69.2, 42.1, 40.8, 25.9, 22.7, 22.2, 10.5, 9.8, 3.2.

Workup

  1. filtrationThe mixture was filtered
  2. customthe solvent evaporated
  3. customto give crude a brown oil, which
  4. customwas purified by column chromatography over silica gel (Heptane-EtOAc gradient)

Sources & evidence

ORD record
ord-41b3f8d5d6ae4e40b3f0871332739d86
Source dataset
uspto-grants-2012_07
Patent number
US08217064B2

Reaction notes

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