2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → Tert-butyl 2-(6-amino-5-fluoropyridin-3-yl)acetate

HRID 1502159Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([NH2:8])=[N:6][CH:7]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Cl-].[C:45]([O:49][C:50](=[O:53])[CH2:51][Zn+])([CH3:48])([CH3:47])[CH3:46]>C1COCC1.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]>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([CH2:51][C:50]([O:49][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:53])=[CH:3][C:4]=1[F:9]

Participants

Conditions

Temperature: 65 °C

Procedure

To 5-bromo-3-fluoropyridin-2-amine (300 mg, 2.0 mmol) in THF (10 mL) was added Pd2(dba)3 (94 mg, 0.10 mmol) and X—PHOS (98 mg, 0.20 mmol), followed by 2-(tert-butoxy)-2-oxoethylzinc chloride solution (10.6 mL, 0.5 M, 5.3 mmol). The reaction mixture was heated at 65° C. over night. The reaction mixture was quenched with NH4Cl, and the aqueous layer was extracted with EtOAc. The organic extracts were washed with brine, dried, and evaporated to give the crude product, which was purified by column chromatography (0-100% EtOAc/hexanes) to give title compound: LC/MS: [(M+1-56)]+=171.5;

Workup

customThe reaction mixture was quenched with NH4Cl
extractionthe aqueous layer was extracted with EtOAc
washThe organic extracts were washed with brine
customdried
customevaporated
customto give the crude product, which
customwas purified by column chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-33c7d61e0ad445e9861c272707bc9403
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206199B2

Reaction notes

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