Oxirane, ((phenylmethoxy)methyl)-, (S)- (9CI) → HCID 68961782, compound

HRID 2116091Notes

Reaction equation

Br[C:2]1[C:3]([O:17][CH3:18])=[C:4]([C:9]2[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:16])[CH:5]=[C:6]([F:8])[CH:7]=1.C([Mg]Cl)(C)C.[Cu]C#N.[CH2:27]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C@H:28]1[O:30][CH2:29]1>O1CCCC1>[CH2:32]([O:31][CH2:27][C@@H:28]([OH:30])[CH2:29][C:2]1[C:3]([O:17][CH3:18])=[C:4]([C:9]2[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:16])[CH:5]=[C:6]([F:8])[CH:7]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-bromo-2′,6′-dichloro-5-fluoro-2-methoxy-biphenyl (2.2 g, 6.3 mmol) in anhydrous tetrahydrofuran at 0° C. was added isopropylmagnesium chloride (3.45 ml, 2.0 M in hexane) and the resulting mixture was allowed to stir at 0° C. for 4 h. The reaction mixture was cooled to −30° C. and copper(I) cyanide (0.28 g, 3.1 mmol) in tetrahydrofuran was added and the reaction mixture was allowed to stir at −30° C. for 1 h. Benzyl(S)-(+)-glycidyl ether (0.48 ml, 3.1 mmol) was then added at −30° C. and the reaction mixture was allowed to warm to room temperature for 12 h. The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate:hexanes 3:7) provided 1.28 g (94%) of (S)-1-benzyloxy-3-(2′,6′-dichlor-5-fluoro-2-methoxybiphenyl-3-yl)propan-2-ol as a colorless oil. HRMS ESI m/e 435.0946 [M−H]−, Calc'd 435.0930; [α]D25=+2.8 (c 8.14 in dimethylsulfoxide).

Workup

temperatureThe reaction mixture was cooled to −30° C.
stirringto stir at −30° C. for 1 h
temperatureto warm to room temperature for 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-6a81a99c6ecb44d2a3ab30e5844a8bb0
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07435837B2

Reaction notes

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