3-Chloro-4-fluoroaniline → methyl N-(3-chloro-4-fluorophenyl)alaninate

HRID 1822172Notes

Reaction equation

HRID 1822172 reaction equation
[C:1]([O:6][CH3:7])(=[O:5])[C:2]([CH3:4])=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][C:15]=1[F:16])[NH2:12].[H][H]>[Pd]>[Cl:8][C:9]1[CH:10]=[C:11]([NH:12][C@H:2]([C:1]([O:6][CH3:7])=[O:5])[CH3:4])[CH:13]=[CH:14][C:15]=1[F:16]

Participants

5

Reactant 3

HCID 97083-Chloro-4-fluoroanilineHCID 11748Methyl pyruvateHCID 178418361HCID 178418361, compound

Product 1

HCID 54503916methyl N-(3-chloro-4-fluorophenyl)alaninate

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Methyl pyruvate (1-1, 42.082 g, 412.201 mmol) and 3-chloro-4-fluoroaniline (1-2, 15.000 g, 103.50 mmol) were combined in a dry pressure tube, and dissolved in cyclohexanes (400 mL). The resulting solution was treated with 10% palladium on activated carbon (7.500 g), and reacted under high pressure hydrogen gas (50 bar) for 24 h. Upon completion, the reaction mixture was filtered through celite and washed 5 times with 40 mL portions of cyclohexanes. The filtrate was concentrated under vacuum. The crude residue was purified by flash column chromotography (SiO2, 0-100% EtOAc/hexanes gradient) to give methyl N-(3-chloro-4-fluorophenyl)alaninate (1-3). 1H NMR (300 MHz, CDCl3) δ 6.94 (dd, J=8.8, 8.8 Hz, 1H), 6.60 (dd, J=6.0, 3.0 Hz, 1H), 6.42 (dd, 8.8, 6.7, 3.0 Hz 1H), 4.13 (q, J=7.0 Hz, 1H), 3.75 (m, 3H), 1.47 (d, J=6.7 Hz, 3H). MS 332.2 found, 332.6 (M+H+) required.

Workup

  1. filtrationUpon completion, the reaction mixture was filtered through celite
  2. washwashed 5 times with 40 mL portions of cyclohexanes
  3. concentrationThe filtrate was concentrated under vacuum
  4. customThe crude residue was purified by flash column chromotography (SiO2, 0-100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-371a5d51ee0e4592b08391f0a4acba4f
Source dataset
uspto-grants-2009_10
Patent number
US07608739B2

Reaction notes

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