Ammonium Chloride → (S)-3-((R,Z)-6-(Benzyloxy)-2-(4-fluoro-3-methylphenoxy)hex-4-enoyl)-4-isopropyloxazolidin-2-one

HRID 1361055Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:30]=[CH:29][C:15]([O:16][CH2:17][C:18]([N:20]2[C@@H:24]([CH:25]([CH3:27])[CH3:26])[CH2:23][O:22][C:21]2=[O:28])=[O:19])=[CH:14][C:13]=1[CH3:31].I[CH2:33][CH:34]=[CH:35][CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[NH4+].[Cl-]>C1COCC1>[CH2:38]([O:37][CH2:36]/[CH:35]=[CH:34]\[CH2:33][C@@H:17]([O:16][C:15]1[CH:29]=[CH:30][C:12]([F:11])=[C:13]([CH3:31])[CH:14]=1)[C:18]([N:20]1[C@@H:24]([CH:25]([CH3:26])[CH3:27])[CH2:23][O:22][C:21]1=[O:28])=[O:19])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

Conditions

Temperature: -70 °C

Procedure

To the solution of lithium bis(trimethylsilyl)amide (1.2 mL, 1.2 mmol, 1M in THF) in anhydrous 20 mL THF at −70° C. was slowly added over 15 minutes (S)-3-(2-(4-fluoro-3-methylphenoxy)acetyl)-4-isopropyloxazolidin-2-one (295 mg, 1.0 mmol) as a solution in 3.0 mL THF. The reaction mixture was stirred for 30 min at −70° C. and then was slowly added a pre-cooled solution of (4-Iodo-but-2-enyloxymethyl)-benzene (576 mg, 2.0 mmol) in 3 mL of THF. The resulting mixture was stirred at −70° C. for 1 h and the temperature was slowly raised over a period of 2 h. The mixture was poured into 20 mL saturated NH4Cl and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (2×20 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the product isolated by Flash column chromatography eluting with 0% to 50% ethyl acetate/hexane to give 294 mg of the title compound as a light yellow oil.

Workup

stirringThe resulting mixture was stirred at −70° C. for 1 h
temperaturethe temperature was slowly raised over a period of 2 h
extractionextracted with ethyl acetate (3×30 mL)
washThe combined organic layers were washed with brine (2×20 mL)
dry with materialdried over Na2SO4
customThe solvent was removed under reduced pressure
customthe product isolated by Flash column chromatography
washeluting with 0% to 50% ethyl acetate/hexane

Sources & evidence

ORD record: ord-2fa142c92cd243b4a208848cbc357c00
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879911B2

Reaction notes

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