Ethyl orthoformate → HCID 178500757, compound

HRID 526157Notes

Reaction equation

HRID 526157 reaction equation
[CH:1]1([C:4](=[O:10])[CH2:5][C:6]([O:8][CH3:9])=[O:7])[CH2:3][CH2:2]1.[CH:11](OCC)(OCC)OCC.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][N:23]=1>>[Cl:21][C:22]1[N:23]=[CH:24][C:25]([NH:28][CH:11]=[C:5]([C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:10])[C:6]([O:8][CH3:9])=[O:7])=[CH:26][CH:27]=1

Participants

4

Reactant 3

HCID 31214Ethyl orthoformateHCID 793055-Amino-2-chloropyridineHCID 101300163-Cyclopropyl-3-Oxopropionic Acid Methyl Ester

Product 1

HCID 178500757HCID 178500757, compoundYield 29.9%

Conditions

Temperature
145 °C

Procedure

A mixture of methyl 3-cyclopropyl-3-oxopropanoate (7.2 g, 50 mmol), triethyl orthoformate (13 mL, 75 mmol) and 2-chloro-5-aminopyridine (6.4 g, 50 mmol) was heated at 145° C. for 3 h in a round bottomed flask that was equipped with a short path distillation apparatus to collect the ethanol generated during the reaction. The reaction was cooled, concentrated and the residue was purified by chromatography (silica, hexanes/ethyl acetate) to afford the desired product (4.2 g, 28%) as a pale yellow oil: 1H NMR (300 MHz, CDCl3) δ 12.78 (d, 12.5 Hz, 1H), 8.40-8.34 (m, 1H), 8.28 (d, J=2.9 Hz, 1H), 7.51-7.44 (m, 1H), 7.35 (d, J=8.6 Hz, 1H), 4.30 (q, J=7.1 Hz, 2H), 3.28-3.18 (m, 1H), 1.36 (t, J=7.1 Hz, 3H), 1.17-1.09 (m, 2H), 1.02-0.86 (m, 2H). ESI MS m/z 281 [M+H]+.

Workup

  1. customwas equipped with a short path distillation apparatus
  2. customto collect the ethanol
  3. customgenerated during the reaction
  4. temperatureThe reaction was cooled
  5. concentrationconcentrated
  6. customthe residue was purified by chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-86e2c02785b542a7933b81a23b0a89a3
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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