Methylamine → HCID 11098956, compound

HRID 1106894Notes

Reaction equation

HRID 1106894 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@H:15]2[CH2:17]O2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1.[CH2:23]([N:25](CC)CC)C.CS(Cl)(=O)=O.CN>C(O)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@H:15]([NH:25][CH3:23])[CH2:17][N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6329MethylamineHCID 8471Triethylamine2×HCID 31268PyrrolidineHCID 31297Methanesulfonyl chlorideHCID 12163517HCID 12163517, compound

Product 1

HCID 11098956HCID 11098956, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of Example 3 (2.80 g, 12.4 mmol) in ethanol (45 mL), pyrrolidine (3.3 mL, 39.5 mmol) was added. The reaction was heated to reflux for 2.5 hours then all volatiles removed in vacuo. This was then dissolved in diethyl ether (60 mL), cooled to 0° C., and flushed with argon. Triethylamine (5.5 mL, 39 mmol) was added followed by methanesulphonyl chloride (1.2 mL, 16 mmol), and the reaction was stirred for 30 minutes. More triethylamine (3.7 mL, 26 mmol) was added, the reaction was warmed to room temperature over 30 minutes, then an aqueous solution of methylamine (40% w/w) (19 mL, 220 mmol) and water (16 mL) were added. After stirring for 18.5 hours, the layers were separated, and the aqueous layer was extracted with diethyl ether (3×100 mL). The combined organics were washed with 5% sodium bicarbonate solution (60 mL), water (60 mL) and brine (60 mL), dried (MgSO4), and the solvent removed in vacuo. Purification by column chromatography (dichloromethane:methanol 9:1→dichloromethane:methanol:ammonia 40:9:1) gave the product as a yellow semi-solid, 9.0 mmol, 72%.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2.5 hours
  3. customall volatiles removed in vacuo
  4. dissolutionThis was then dissolved in diethyl ether (60 mL)
  5. customflushed with argon
  6. temperaturethe reaction was warmed to room temperature over 30 minutes
  7. stirringAfter stirring for 18.5 hours
  8. customthe layers were separated
  9. extractionthe aqueous layer was extracted with diethyl ether (3×100 mL)
  10. washThe combined organics were washed with 5% sodium bicarbonate solution (60 mL), water (60 mL) and brine (60 mL)
  11. dry with materialdried (MgSO4)
  12. customthe solvent removed in vacuo
  13. customPurification by column chromatography (dichloromethane:methanol 9:1→dichloromethane:methanol:ammonia 40:9:1)

Sources & evidence

ORD record
ord-2175e9d1d74d46d69d92cbc1f2c5a592
Source dataset
uspto-grants-2000_05
Patent number
US06057357

Reaction notes

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