1,1,1-Trifluoro-3-iodopropane → 2-Isopropyl-3,6-dimethoxy-5-(3,3,3-trifluoro-propyl)-2,5-dihydro-pyrazine

HRID 417709Notes

Reaction equation

[CH:1]([CH:4]1[C:9]([O:10][CH3:11])=[N:8][CH2:7][C:6]([O:12][CH3:13])=[N:5]1)([CH3:3])[CH3:2].C([Li])CCC.I[CH2:20][CH2:21][C:22]([F:25])([F:24])[F:23]>C1COCC1.C(OCC)(=O)C>[CH:1]([CH:4]1[C:9]([O:10][CH3:11])=[N:8][CH:7]([CH2:20][CH2:21][C:22]([F:25])([F:24])[F:23])[C:6]([O:12][CH3:13])=[N:5]1)([CH3:3])[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of 2-isopropyl-3,6-dimethoxy-2,5-dihydro-pyrazine (1 mL, 5.58 mmol) in THF (13.5 mL) under argon at −78° C. was added a solution of n-butyllithium (2.5 M, 2.3 mL, 5.75 mmol). The solution was stirred at −78° C. for 30 minutes. A solution of 1-Iodo-3,3,3-trifluoropropane (925 μL, 5.87 mmol) in THF (11.5 mL) was added slowly. The resulting solution was stirred at −78° C. for 5 hours, warmed to room temperature and diluted with ethyl acetate. The organic layer was washed successively with saturated aqueous NH4Cl solution, water and brine. The organic layer was then dried (MgSO4), concentrated and purified by flash chromatography to yield 2-Isopropyl-3,6-dimethoxy-5-(3,3,3-trifluoro-propyl)-2,5-dihydro-pyrazine (915 mg, 59%). 1H-NMR: 400 MHz, (CDCl3) δ: 4.04-3.99 (m, 1H), 3.98-3.95 (m, 1H), 3.71 (s, 3H), 3.68 (s, 3H), 2.29-2.20 (m, 1H), 2.18-2.04 (m, 3H), 1.94-1.84 (m, 1H), 1.03 (d, J=6.9 Hz, 3H), 0.71 (d, J=6.8 Hz, 3H) ppm.

Workup

stirringThe resulting solution was stirred at −78° C. for 5 hours
temperaturewarmed to room temperature
washThe organic layer was washed successively with saturated aqueous NH4Cl solution, water and brine
dry with materialThe organic layer was then dried (MgSO4)
concentrationconcentrated
custompurified by flash chromatography

Sources & evidence

ORD record: ord-595963bbda0140109dbe4f59f42aa937
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088368B2

Reaction notes

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