Lithium Hexamethyldisilazide → (R)-3-((S,E)-2-(4-fluoro-3,5-dimethylbenzyl)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one

HRID 1158129Notes

Reaction equation

[CH3:1][CH:2]([CH3:24])/[CH:3]=[CH:4]/[CH2:5][CH2:6][CH2:7][CH2:8][C:9]([N:11]1[C@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][C:12]1=[O:23])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([CH3:45])[C:43]=1[F:44])[CH2:39]Br>C1COCC1>[F:44][C:43]1[C:36]([CH3:35])=[CH:37][C:38]([CH2:39][C@H:8]([CH2:7][CH2:6][CH2:5]/[CH:4]=[CH:3]/[CH:2]([CH3:24])[CH3:1])[C:9]([N:11]2[C@H:15]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:14][O:13][C:12]2=[O:23])=[O:10])=[CH:41][C:42]=1[CH3:45]

Participants

Conditions

Temperature: -78 °C

Procedure

To a cooled (−78° C.) solution of (R)-3-((E)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one (2.000 g, 6.071 mmol) in 40 mL of THF, was added LiHMDS (9.1 mL, 9.1 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (1.450 g, 6.678 mmol) in 10 mL of THF was added. After being stirred at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h, and then quenched with 80 mL of NH4Cl solution and extracted with dichloromethane (60 mL×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (1.925 g, 68% yield). GC-MS: tR=8.8 min; m/z 465 (M+).

Workup

stirringAfter being stirred at −78° C. for 1 h the reaction mixture
temperaturewas warmed to room temperature for 2 h
customquenched with 80 mL of NH4Cl solution
extractionextracted with dichloromethane (60 mL×3)
dry with materialThe combined organic extracts were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe product was isolated by Flash column chromatography (silica gel column)
washeluting with 0-100% dichloromethane/hexanes

Sources & evidence

ORD record: ord-7d22810b2f6c470ebba722897d8a8e1e
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07807720B2

Reaction notes

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