Ethanol → 1-{5-Chloro-2-ethoxy-4-fluoro-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethanone

HRID 511037Notes

Reaction equation

[Cl:1][C:2]1[C:3]([F:22])=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:17]=2)[C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH2:23](O)[CH3:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:1][C:2]1[C:3]([F:22])=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:17]=2)[C:5]([O:11][CH2:23][CH3:24])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 1-{5-chloro-4-fluoro-2-hydroxy-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethanone (1.3 g, 3.6 mmol) in THF (32 mL) was treated with ethanol (0.28 mL, 4.73 mmol) and triphenylphosphine (1.3 g, 5.1 mmol). The reaction mixture was cooled to 0° C., treated with diisopropyl azodicarboxylate (1.1 mL, 5.5 mmol) dropwise, and stirred at 20° C. for 1 hour. The reaction mixture was concentrated to remove most of the THF, diluted with EtOAc, washed with saturated sodium bicarbonate, water, brine, dried over sodium sulfate, filtered and concentrated to a crude residue which was purified by flash column chromatography using EtOAc in hexanes (15%-65%) to give the desired product (1.2 g, 87%). LCMS for C16H16ClFNO4S (M+H)+: m/z=372.0. Found: 372.1.

Workup

concentrationThe reaction mixture was concentrated
customto remove most of the THF
additiondiluted with EtOAc
washwashed with saturated sodium bicarbonate, water, brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated to a crude residue which
customwas purified by flash column chromatography

Sources & evidence

ORD record: ord-eef02a5ab3824dab98f37202f461d83d
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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