4-(5-Fluoro-4-iodo-2-methylphenyl)-2-methylpyridine → Tert-butyl 2-(2-fluoro-5-methyl-4-(2-methylpyridin-4-yl)phenyl)acetate

HRID 1036257Notes

Reaction equation

[F:1][C:2]1[C:3](I)=[CH:4][C:5]([CH3:15])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)[CH:7]=1.[Cl-].[C:18]([O:22][C:23](=[O:26])[CH2:24][Zn+])([CH3:21])([CH3:20])[CH3:19]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2].C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)[C:5]([CH3:15])=[CH:4][C:3]=1[CH2:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:26]

Participants

Conditions

Temperature: 70 °C

Procedure

To a seal tube charged with 4-(5-fluoro-4-iodo-2-methylphenyl)-2-methylpyridine 191-4 (200 mg, 0.6 mmol), Pd2(dba)3 (28 mg, 0.03 mmol), and Q-Phos (21 mg, 0.03 mmol) was added anhydrous THF (2.5 mL). The reaction vessel was flushed with nitrogen and (2-tert-butoxy-2-oxoethyl)zinc(II) chloride (0.5 M in ether, 1.34 mL, 0.67 mmol) was added subsequently. The reaction was heated to 70° C. for 12 hours. The solvent was removed by rotary evaporation and the residue was purified by silica gel flash chromatography, eluted with 50% ethyl acetate in hexane to give tert-butyl 2-(2-fluoro-5-methyl-4-(2-methylpyridin-4-yl)phenyl)acetate 191-5. MS m/z 316.10 (M+1).

Workup

additionwas added subsequently
customThe solvent was removed by rotary evaporation
customthe residue was purified by silica gel flash chromatography
washeluted with 50% ethyl acetate in hexane

Sources & evidence

ORD record: ord-45a12c243f7a421696f2e15bcc091604
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546396B2

Reaction notes

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