2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → Tert-butyl 2-(4-cyano-2-fluorophenyl)acetate

HRID 578922Notes

Reaction equation

Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[F:10].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.[Cl-].[C:40]([O:44][C:45](=[O:48])[CH2:46][Zn+])([CH3:43])([CH3:42])[CH3:41]>C1COCC1.C1(C)C=CC=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]>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([CH2:46][C:45]([O:44][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:48])=[C:3]([F:10])[CH:4]=1)#[N:7]

Participants

Conditions

Temperature: 50 °C

Procedure

Combined 4-bromo-3-fluorobenzonitrile (2.0 g, 10.00 mmol), Pd(dba)2 (0.287 g, 0.500 mmol), and 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (0.394 g, 1.000 mmol) in THF (60 mL) with nitrogen purge. Then (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (0.5M, 30 mL, 15.0 mmol) was added via syringe. The reaction mixture was heated in an oil bath at 50° C. for 18 hours and then was adsorbed onto silica gel (11 g) and purified by flash chromatography using an eluent of 1:1 heptane/EtOAc on an 80 g silica gel column (Single Step™) to give a residue. The residue was dissolved in toluene (0.5 mL) and purified by flash chromatography using a gradient eluent of heptane/EtOAc (0-25% EtOAc) on an 80 g silica gel column (Single Step™) to give the title compound (1.752 g, 74.5% yield) as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 1.45 (s, 9 H) 3.64 (d, J=1.26 Hz, 2 H) 7.36 (dd, J=8.97, 1.39 Hz, 1 H) 7.40 (d, J=7.07 Hz, 1 H) 7.42-7.45 (m, 1 H). MS m/z [M+H]+ 236.1.

Workup

custompurified by flash chromatography
customto give a residue
custompurified by flash chromatography

Sources & evidence

ORD record: ord-1423aba2e6fb440f86321075e20648d3
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040522B2

Reaction notes

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