N-methyl-2-pyrrolidone → HCID 90387132, compound

HRID 1476868Notes

Reaction equation

HRID 1476868 reaction equation
CN1CCCC1=O.[OH:8][C@H:9]1[C@H:13]([CH3:14])[CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]1.[H-].[Na+].Cl[C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[C:27]([Cl:35])[N:26]=1>O>[Cl:35][C:27]1[N:26]=[C:25]([O:8][C@H:9]2[C@H:13]([CH3:14])[CH2:12][N:11]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:10]2)[C:34]2[C:29]([CH:28]=1)=[CH:30][CH:31]=[CH:32][CH:33]=2

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 24758Sodium hydrideHCID 2986251,3-DichloroisoquinolineHCID 53302312tert-butyl (3S,4R)-3-hydroxy-4-Methylpyrrolidine-1-carboxylate

Product 1

HCID 90387132HCID 90387132, compoundYield 58.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a 25 mL microwave vial was added N-methyl-2-pyrrolidinone (10.00 mL) and tert-butyl trans-3-hydroxy-4-methylpyrrolidine-1-carboxylate (1.118 g, 5.55 mmol). The mixture was cooled to 0° C. under a nitrogen atmosphere. To this mixture was added portion-wise NaH (60% suspension in mineral oil, 0.202 g, 5.05 mmol). After 5 minutes the mixture was allowed to warm to RT and was stirred for 10 minutes. Next, 1,3-dichloroisoquinoline (1 g, 5.05 mmol) was added and the reaction mixture was heated in a microwave reactor at 135° C. for 30 minutes. The reaction mixture was subsequently diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and concentrated onto silica. The crude product was purified by flash column chromatography (SiO2) eluting with a gradient of 5-50% heptane in EtOAc to give the title compound as a white solid (1.066 g, 58.2%). 1H NMR (500 MHz, CDCl3) δ ppm 1.16 (d, 3H), 1.48 (s, 9H), 2.60 (br s, 1H), 3.23 (br s, 1H), 3.49 (br s, 1H), 3.74 (br s, 1H), 3.94 (br s, 1H), 5.38 (br s, 1H), 7.23-7.32 (m, 1H), 7.51 (ddd, 1H), 7.61-7.71 (m, 2H), 8.17 (d, 1H); ESI-MS m/z [M+H]+ 307.6.

Workup

  1. temperatureto warm to RT
  2. temperaturethe reaction mixture was heated in a microwave reactor at 135° C. for 30 minutes
  3. extractionextracted with EtOAc (3×100 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated onto silica
  7. customThe crude product was purified by flash column chromatography (SiO2)
  8. washeluting with a gradient of 5-50% heptane in EtOAc

Sources & evidence

ORD record
ord-43651aa1f76e432a816dc7b673402862
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

Loading…