Dimethylformamide → (S)-ethyl 2-tert-butoxy-2-(6-cyano-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

HRID 926148Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17](Cl)[CH:18]=2)[C:13]=1[OH:25])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].[CH3:31][N:32](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:31]#[N:32])[CH:18]=2)[C:13]=1[OH:25])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (S)-ethyl 2-tert-butoxy-2-(6-chloro-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate (0.2186 g, 0.593 mmol), zinc(II) cyanide (0.0695 g, 0.593 mmol), XPhos Palladacycle (0.044 g, 0.0593 mmol) and sodium bicarbonate (0.005 g, 0.0593 mmol) in anhydrous DMF (3.0 mL) was heated in a microwave at 100° C. for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The Combined organic layer was washed with 5% lithium chloride solution, brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 15% ethyl acetate/hexanes) to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C20H21FNO4: 358.2. Found: 357.9.

Workup

extractionextracted with ethyl acetate (2×)
washThe Combined organic layer was washed with 5% lithium chloride solution, brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
custompurified by flash column chromatography (silica gel, 0 to 15% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-08fec636aa0e4ad893de26e4626257ab
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284323B2

Reaction notes

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