Triethylamine → HCID 89649640, compound

HRID 2207658Notes

Reaction equation

HRID 2207658 reaction equation
[CH:1](S(C1C=CC=CC=1)(=O)=O)=[CH2:2].[NH2:12][CH:13]1[CH2:17][CH2:16][N:15]([CH3:18])[C:14]1=[O:19].[Br:20][C:21]1[C:26]([CH2:27][CH3:28])=[CH:25][N:24]=[C:23]([CH:29]=O)[CH:22]=1.[O-]S(C(F)(F)F)(=O)=O.[Ca+2].[O-]S(C(F)(F)F)(=O)=O.C(N(CC)CC)C.CC(C)([O-])C.[K+]>CO>[Br:20][C:21]1[C:26]([CH2:27][CH3:28])=[CH:25][N:24]=[C:23]([C:29]2[CH2:2][CH2:1][C:13]3([CH2:17][CH2:16][N:15]([CH3:18])[C:14]3=[O:19])[N:12]=2)[CH:22]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 79664Phenyl vinyl sulfoneHCID 2734307Methanesulfonic acid, 1,1,1-trifluoro-, calcium salt (2:1)HCID 23665647Potassium tert-butoxideHCID 457911333-Amino-1-methylpyrrolidin-2-oneHCID 89649386HCID 89649386, compound

Product 1

HCID 89649640HCID 89649640, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-10 °C

Procedure

To a stirred solution of phenyl vinyl sulfone (7307.08 mg, 43.44 mmol) in methanol (80 mL) was added 3-amino-1-methyl-pyrrolidin-2-one (4958.41 mg, 43.44 mmol), 4-bromo-5-ethyl-pyridine-2-carbaldehyde (CAS: 1256833-98-3) (9300 mg, 43.44 mmol) and calcium triflate (734.57 mg, 2.17 mmol). The reaction was stirred for 10 minutes, and then the reaction was cooled to −10° C., and then triethylamine (6.04 mL, 43.44 mmol) was added dropwise. The reaction was then stirred at room temperature for 4 hours. The reaction was concentrated in vacuo, and redissolved in THF (150 mL). The reaction was cooled to 00° C., and to the reaction mixture was added potassium tert-butoxide (14622.41 mg, 130.31 mmol) portionwise. The reaction was then stirred for 2 hours while allowing to warm to room temperature. The reaction was then filtered through celite, and the celite was washed with DCM (150 mL). The filtrate was then concentrated in vacuo. The residue was purified by column chromatography over silica (340 g, Biotage SNAP cartridge), eluting with EtOAc:isohexane from 0% to 100%. Fractions containing the desired product were combined and concentrated in vacuo to give 2-(4-bromo-5-ethyl-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one (D121) (3091 mg, 9.1931 mmol, 21.2% yield) as a brown oil approximately 85% pure and used directly in the next step;

Workup

  1. stirringThe reaction was then stirred at room temperature for 4 hours
  2. concentrationThe reaction was concentrated in vacuo
  3. dissolutionredissolved in THF (150 mL)
  4. temperatureThe reaction was cooled to 00° C
  5. stirringThe reaction was then stirred for 2 hours
  6. temperatureto warm to room temperature
  7. filtrationThe reaction was then filtered through celite
  8. washthe celite was washed with DCM (150 mL)
  9. concentrationThe filtrate was then concentrated in vacuo
  10. customThe residue was purified by column chromatography over silica (340 g, Biotage SNAP cartridge)
  11. washeluting with EtOAc
  12. additionFractions containing the desired product
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-00053ce0e8a846c2a5ae53c28047c4a3
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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