2-Bromo-4-fluoroanisole → HCID 68964462, compound

HRID 2116090Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4](Br)[CH:3]=1.C([Li])CCC.[CH2:16]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C@H:17]1[O:19][CH2:18]1>O1CCCC1.[Cu]Br.CSC.B(F)(F)F.CCOCC>[CH2:21]([O:20][CH2:16][C@@H:17]([OH:19])[CH2:18][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[O:8][CH3:9])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 4-fluoro-2-bromanisole (12.6 ml, 0.1 mol) in anhydrous tetrahydrofuran at −78° C. was added n-butyllithium (39 ml, 2.5 M in hexane) and the resulting mixture was allowed to stir at −78° C. for 3 h. Copper(I) bromide-dimethylsulfide (10.0 g, 0.05 mol) was then added at −78° C. and the reaction mixture was allowed to warm to 40° C. over 2 h. Benzyl(S)-(+)-glycidyl ether (3.71 ml, 0.025 mol) was added at −60° C. followed by boron trifluoride diethyl etherate (0.15 ml, 1.2 mmol) and the reaction mixture was allowed to warm to room temperature over 12 h. The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate:hexanes 3:7) afforded 5.0 g (70%) of (S)-1-benzyloxy-3-(5-fluoro-2-methoxy-phenyl)propan-2-ol as a colorless oil. HRMS ESI m/e 308.1666 [M+NH4]+, Calc'd m/e 308.1662 [M+NH4]+; [α]D25=+8.1 (c 0.89% in methanol).

Workup

temperatureto warm to 40° C. over 2 h
temperatureto warm to room temperature over 12 h
customThe solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate:hexanes 3:7)

Sources & evidence

ORD record: ord-1b66b6e9df4e45fd9a01daa0431bf9bb
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07435837B2

Reaction notes

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