3-Pentanol → {4-[6-Ethyl-5-(ethylpropoxy)-3-methoxypyrazin-2-yl]-3-methoxyphenoxy}trifluoromethane

HRID 1270332Notes

Reaction equation

[CH3:1][CH2:2][CH:3]([OH:6])[CH2:4][CH3:5].[H-].[Na+].Br[C:10]1[N:11]=[C:12]([O:31][CH3:32])[C:13]([C:18]2[CH:28]=[CH:27][C:21]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:20][C:19]=2[O:29][CH3:30])=[N:14][C:15]=1[CH2:16][CH3:17]>C1COCC1>[CH2:16]([C:15]1[N:14]=[C:13]([C:18]2[CH:28]=[CH:27][C:21]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:20][C:19]=2[O:29][CH3:30])[C:12]([O:31][CH3:32])=[N:11][C:10]=1[O:6][CH:3]([CH2:4][CH3:5])[CH2:2][CH3:1])[CH3:17]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 3-pentanol (88 mg, 1 mmol) in THF (1 mL) is added 60% sodium hydride (12 mg, 0.3 mmol) and after 0.5 h [4-(5-bromo-6-ethyl-3-methoxypyrazin-2-yl)-3-methoxyphenoxy]trifluoromethane (41 mg, 0.1 mmol) is added. The mixture is heated to 50° C. for 12 h, cooled and partitioned between ethyl acetate and water. The organic layer is washed with water, brine, dried (sodium sulfate), filtered and concentrated. The residue is purified by preparative TLC eluting with 50% ether in hexanes to give {4-[6-Ethyl-5-(ethylpropoxy)-3-methoxypyrazin-2-yl]-3-methoxyphenoxy}trifluoromethane, a colorless oil (19 mg). NMR (CDCL3, 400 MHz) □0.98 (t, 6H), 1.22 (t, 3H), 1.78 (m, 4H) 2.80 (q, 2H), 3.80 (s, 3H), 3.88 (s, 3H), 5.05 (quintet, 1H), 6.8 (s, 1H), 6.90 (d, 1H), 7.37 (d, 1H); MS 345 (M+1).

Workup

temperaturecooled
custompartitioned between ethyl acetate and water
washThe organic layer is washed with water, brine
dry with materialdried (sodium sulfate)
filtrationfiltered
concentrationconcentrated
customThe residue is purified by preparative TLC
washeluting with 50% ether in hexanes

Sources & evidence

ORD record: ord-9f6c13d64fa647cb9e7606100045ec16
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07202250B2

Reaction notes

Loading…