4-Phenoxybenzaldehyde → (3-Chloropyrazin-2-yl)-(4-phenoxyphenyl)-methanol

HRID 449024Notes

Reaction equation

[Li]CCCC.[Cl:6][C:7]1[CH:12]=[N:11][CH:10]=[CH:9][N:8]=1.[CH:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]=[O:27])=[CH:22][CH:21]=2)=[CH:15][CH:14]=1>C1COCC1>[Cl:6][C:7]1[C:12]([CH:26]([C:23]2[CH:24]=[CH:25][C:20]([O:19][C:16]3[CH:15]=[CH:14][CH:13]=[CH:18][CH:17]=3)=[CH:21][CH:22]=2)[OH:27])=[N:11][CH:10]=[CH:9][N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2.5 M of n-BuLi in hexanes (10 mL) in THF (50 mL) was added 2,2,66-tetramethyl-piperidine (5.3 mL, 0.031 mol) slowly at −78° C. The cooling bath was replaced by an ice-water bath for 30 min and the solution was re-cooled to −78° C. After 5 min a solution of 2-chloropyrazine (2.3 mL, 0.026 mol) in THF (10 mL) is added. The reaction mixture turned brown in color. After 10 min, 4-formyldiphenyl ether (6.2 g, 0.031 mol) was added slowly. The reaction mixture was stirred at −78° C. for 2.5 h. The reaction mixture was quenched using sat. aq. NH4Cl at −78° C. After warming up to rt, the reaction mixture was concentrated under vacuo and purified by flash column chromatography (eluting with 10% EtOAc in hexanes) to afford the title compound. 1H NMR (400 MHz, CDCl3): δ 6.02 (s, 1H), 6.93-6.98 (m, 2H), 7.00 (d, J=7.58 Hz, 2H), 7.12 (t, J=7.33 Hz, 1H), 7.29-7.37 (m, 4H), 8.39 (d, J=2.53 Hz, 1H), 8.58 (d, J=2.53 Hz, 1H). MS (ES+): m/z 295.08 (100)[M-18]. HPLC: tR=3.46 min (Open lynx, polar—5 min).

Workup

waitAfter 10 min
customThe reaction mixture was quenched
customat −78° C
temperatureAfter warming up to rt
concentrationthe reaction mixture was concentrated under vacuo
custompurified by flash column chromatography (eluting with 10% EtOAc in hexanes)

Sources & evidence

ORD record: ord-9667dd499aa8455e9c991ea3752479b9
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481733B2

Reaction notes

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