Sodium Carbonate → 2-(3-Amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

HRID 1183611Notes

Reaction equation

HRID 1183611 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH:5]([C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[C:13]([O:20][CH2:21][CH:22]2[CH2:24][CH2:23]2)=[C:12]([N+:25]([O-])=O)[CH:11]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.Cl.[Pd]>[CH2:1]([O:3][C:4](=[O:28])[CH:5]([C:10]1[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[C:13]([O:20][CH2:21][CH:22]2[CH2:24][CH2:23]2)=[C:12]([NH2:25])[CH:11]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

6

Reactant 2

HCID 10340Sodium CarbonateHCID 579956202-(4-Cyclopropylmethoxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

Product 1

HCID 687331102-(3-Amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl esterYield 51.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

A mixture of 2-(4-cyclopropylmethoxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (1.85 g, 4.59 mmol) and Pd/C (1.85 g) in ethanol and 1 N HCl (4.60 mL) was hydrogenated under 36 psi H2 in a Parr apparatus. After 4 h, the reaction mixture was filtered through Celite 521®. The filtrate was concentrated under reduced pressure to give a yellow oil. The residue was treated with an aqueous solution of sodium carbonate (3 g in 100 mL of water) and the resulting solution was extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give a brown oil, which was purified by silica-gel flash chromatography eluting with a gradient of heptane/ethyl acetate (from 10:1 to 2:1) to give 2-(3-amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (0.88 g, 51%) as a light pink oil: 1H NMR (300 MHz, CDCl3): δ 6.83 (s, 1H), 6.80 (s, 1H), 4.04 (m, 2H), 3.85 (s, 2H), 3.66 (d, 2H, J=6.9 Hz), 3.45 (t, 1H, J=7.8 Hz), 1.84 (m, 1H), 1.49 (m, 1H), 1.39 (m, 1H), 1.22 (m, 1H), 1.14 (t, 3H, J=7.2 Hz), 0.82 (m, 6H), 0.56 (d, 2H, J=7.5 Hz), 0.27 (d, 2H, J=4.5 Hz); 13C NMR (75 MHz, CDCl3): δ 173.61, 142.71, 141.25, 135.51, 123.75 (q, J=30 Hz), 123.52 (q, J=271 Hz), 118.46, 115.52 (q, J=5 Hz), 77.88, 60.70, 49.03, 42.53, 25.86, 22.40, 22.31, 14.07, 10.98, 3.19.

Workup

  1. filtrationthe reaction mixture was filtered through Celite 521®
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customto give a yellow oil
  4. extractionthe resulting solution was extracted with ethyl acetate (100 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a brown oil, which
  8. customwas purified by silica-gel flash chromatography
  9. washeluting with a gradient of heptane/ethyl acetate (from 10:1 to 2:1)

Sources & evidence

ORD record
ord-8036cd126782447990392d4d8947c625
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

Loading…