(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine → 1,4-Bis((2R,5S)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-pyrazinyl)-but-2-yne

HRID 976016

Reaction equation

[CH3:1][O:2][C:3]1[C@@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.[Li][CH2:15][CH2:16][CH2:17][CH3:18].[CH3:19][O:20][C:21]1[CH:22]([CH:29]([CH3:31])[CH3:30])[N:23]=[C:24]([O:27][CH3:28])[CH2:25][N:26]=1>C1COCC1>[CH3:1][O:2][C:3]1[C@@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[C@H:7]([CH2:18][C:17]#[C:16][CH2:15][C@H:25]2[C:24]([O:27][CH3:28])=[N:23][C@H:22]([CH:29]([CH3:31])[CH3:30])[C:21]([O:20][CH3:19])=[N:26]2)[N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

(2R)-(-)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine 2.76 g (15mmol) was dissolved in 100 ml dry THF and cooled to -78° C., then 9.5 ml of a 1.6M solution BuLi (15 mmol) was added dropwise with stirring. After 1 hour 0.92 g (7.5 mmol) of 1,4-dichloro-2,3-butyne was introduced slowly. TLC and gas chromatography (GC) of the reaction mixture 1 hour later showed substantial amounts of unreacted 2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine and the monoalkylated product. The reaction was allowed to continue overnight and reach ambient temperature gradually. THF was evaporated off under reduced pressure and the residue partitioned between ether and water. The water phase was extracted twice with ether, dried (MgSO4) and evaporated. Kugelrohr distillation of the reaction mixture to give 2.3g (77%) pure product.

Workup

customreach ambient temperature
customTHF was evaporated off under reduced pressure
customthe residue partitioned between ether and water
extractionThe water phase was extracted twice with ether
dry with materialdried (MgSO4)
customevaporated
distillationKugelrohr distillation of the reaction mixture

Sources & evidence

ORD record: ord-06cb4186efa54d49b3169c4ce264d158
Source dataset: uspto-grants-1997_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05610141

Linked notes

Loading…