Acrylonitrile → HCID 86723178, compound

HRID 572025Notes

Reaction equation

HRID 572025 reaction equation
Cl.[OH:2][C@H:3]1[CH2:7][NH:6][C@H:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:4]1.[C:12](#[N:15])[CH:13]=[CH2:14].[OH-].[K+]>O>[C:12]([CH2:13][CH2:14][N:6]1[CH2:7][C@H:3]([OH:2])[CH2:4][C@H:5]1[C:8]([O:10][CH3:11])=[O:9])#[N:15]

Participants

5

Reactant 3

HCID 7855AcrylonitrileHCID 14797Potassium HydroxideHCID 114353194-Hydroxy-L-proline methyl ester hydrochloride

Product 1

HCID 86723178HCID 86723178, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of methyl (4R)-4-hydroxy-L-prolinate hydrochloride (4.53 g, 25 mmol) in water (10 mL) was added acrylonitrile (6.63 g, 125 mmol). The mixture was stirred while heating at 50° C., and a solution of potassium hydroxide (1.403 g, 25 mmol) in water (15 mL) was added dropwise. The resulting mixture was heated to 70° C. and stirred for two hours. The cooled mixture was extracted with diethyl ether (4×25 mL). The combined ether extracts were dried with MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using a solvent gradient of 2-5% methanol in dichloromethane to obtain desired the title compound as colorless oil (2.3 g, 46%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.95-4.87 (m, 1H), 4.26-4.17 (m, 1H), 3.62 (s, 3H), 3.50 (t, J=7.6, 1H), 3.27-3.15 (m, 1H), 2.98-2.87 (m, 1H), 2.76-2.66 (m, 1H), 2.67-2.56 (m, 2H), 2.41-2.33 (m, 1H), 1.99 (ddd, J=12.8, 7.4, 6.4, 1H), 1.93-1.83 (m, 1H); MS (ESI) m/z 199 (M+H)+.

Workup

  1. temperatureThe resulting mixture was heated to 70° C.
  2. stirringstirred for two hours
  3. extractionThe cooled mixture was extracted with diethyl ether (4×25 mL)
  4. dry with materialThe combined ether extracts were dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel using a solvent gradient of 2-5% methanol in dichloromethane
  8. customto obtain

Sources & evidence

ORD record
ord-a2ce6613da83461582dcdf9de7a7b4d3
Source dataset
uspto-grants-2015_05
Patent number
US09029361B2

Reaction notes

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