4-Toluenesulfonyl chloride → tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 589862Notes

Reaction equation

HRID 589862 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=O)[CH:10](C([O-])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Na+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.Cl[C:32](=[CH2:35])[C:33]#[N:34].C(N(CC)CC)C>ClCCl.O>[C:33]([C:32]1[CH:35]=[CH:14][N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C:10]=12)#[N:34]

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 701982-ChloroacrylonitrileHCID 59437097Sodium 4-(tert-butoxycarbonyl)-1-formylpiperazine-2-carboxylate

Product 1

HCID 86680813tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylateYield 69.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution under nitrogen of 28.7 g (102 mmol) of sodium 4-(tert-butyloxycarbonyl)-1-formylpiperazine-2-carboxylate (CAS 1108698-36-7) in 1 l of dichloromethane are added 21.5 g (113 mmol) of p-toluenesulfonyl chloride. After stirring for 40 minutes, 8.2 ml (102 mmol) of 2-chloroacrylonitrile are added. After stirring for 40 minutes, 32.8 ml (235 mmol) of triethylamine are added dropwise and the mixture is stirred overnight at room temperature, and then refluxed for 1 hour. The solution is then cooled to room temperature. 150 ml of water are added. The organic phase is separated out by settling, washed twice with 100 ml of water, dried over sodium sulfate and filtered, and concentrated under reduced pressure. The residue obtained is chromatographed on a column of silica gel, eluting with a mixture of 0 to 10% ethyl acetate in dichloromethane, to give 17.5 g of tert-butyl 8-cyano-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after dissolving in a mixture of cyclohexane and dichloromethane and then precipitating by slow concentration and drying under reduced pressure.

Workup

  1. stirringAfter stirring for 40 minutes
  2. stirringthe mixture is stirred overnight at room temperature
  3. temperaturerefluxed for 1 hour
  4. customThe organic phase is separated out
  5. washwashed twice with 100 ml of water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue obtained
  10. customis chromatographed on a column of silica gel
  11. washeluting with a mixture of 0 to 10% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-bb8de5eb08654977bc4709b83a03cefb
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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