p-Toluenesulfonic acid → HCID 178472044, compound

HRID 600865Notes

Reaction equation

HRID 600865 reaction equation
[Cl:1][C:2]1[N:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:3]=1[C:4]([C:6](=[CH:12]OCC)[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:32][C@H:33]1[CH2:35][C@H:34]1[NH2:36].C(N(CC)CC)C>ClCCl.C(OCC)(=O)C>[Cl:1][C:2]1[N:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:3]=1[C:4]([C:6](=[CH:12][NH:36][C@@H:34]1[CH2:35][C@@H:33]1[F:32])[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 10313105(1R,2S)-2-Fluorocyclopropan-1-amineHCID 54146668Ethyl 2-(2,6-dichloropyridine-3-carbonyl)-3-ethoxyprop-2-enoate

Product 1

HCID 178472044HCID 178472044, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

Next, this crude ethyl 2-(2,6-dichloronicotinoyl)-3-ethoxyacrylate (2.11 g, 6.62 mmol) and the para-toluenesulfonic acid salt of 2-(S)-fluoro-1-(R)-cyclopropylamine (2.45 g, 9.91 mmol) were suspended in dichloromethane (30 ml), and triethylamine (2.77 ml, 19.87 mmol) was added dropwise gradually thereto while stirring at −15° C. After completion of dripping, the reaction solution was stirred at room temperature for 15 hours. After adding ethyl acetate (100 ml) to the reaction solution, the organic layer was washed with a 10% aqueous citric acid solution (80 ml), saturated sodium bicarbonate water (80 ml), and saturated saline solution (80 ml), in that order, and then dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, and 2.10 g (90%, 2 processes) of the title compound was thereby obtained as a yellowish-brown, oily substance (E/Z mixture). This resulting substance was used in the subsequent reaction without further purification.

Workup

  1. stirringthe reaction solution was stirred at room temperature for 15 hours
  2. washthe organic layer was washed with a 10% aqueous citric acid solution (80 ml), saturated sodium bicarbonate water (80 ml), and saturated saline solution (80 ml), in that order
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtering
  5. concentrationthe filtrate was concentrated under a reduced pressure, and 2.10 g (90%, 2 processes) of the title compound
  6. customwas thereby obtained as a yellowish-brown, oily substance (E/Z mixture)
  7. customThis resulting substance was used in the subsequent reaction without further purification

Sources & evidence

ORD record
ord-ec391f2c158c4e1eb9366ef3019cd7b5
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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