2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → HCID 178480266, compound

HRID 452994Notes

Reaction equation

HRID 452994 reaction equation
[Br-].[C:2]([O:6][C:7](=[O:10])[CH2:8][Zn+])([CH3:5])([CH3:4])[CH3:3].Br[C:12]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:13]=1[C:14](/[N:16]=[C:17]1/[N:18]([CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][O:29]2)[N:19]([CH3:26])[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:21]/1)=[O:15].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:22]([C:20]1[N:19]([CH3:26])[N:18]([CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][O:29]2)/[C:17](=[N:16]/[C:14]([C:13]2[CH:33]=[C:34]([C:37]([F:38])([F:39])[F:40])[CH:35]=[CH:36][C:12]=2[CH2:8][C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:10])=[O:15])/[CH:21]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 3

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 178451181HCID 178451181, compoundHCID 178480265HCID 178480265, compound

Product 1

HCID 178480266HCID 178480266, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (2-tert-butoxy-2-oxoethyl)zinc(II) bromide (2.13 mL, 1.07 mmol) in ether (3 mL) was added to a mixture of Example 88 (260 mg, 0.532 mmol), palladium acetate (12.0 mg, 0.053 mmol), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (82 mg, 0.20 mmol). The mixture was stirred at 50° C. overnight then quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (3×10 mL). The organic extracts were combined, washed with water, dried (MgSO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 15-100% solvent A in hexanes, solvent A=10:1:0.5 ethyl acetate:methanol:triethyl amine) to afford the title compound (0.19 g, 0.363 mmol, 68.2% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.41 (s, 9H) 1.42 (s, 9H) 1.72-1.88 (m, 3H) 2.00-2.10 (m, 1H) 3.62 (q, J=7.27 Hz, 1H) 3.68-3.82 (m, 2H) 3.87 (s, 3H) 4.19 (d, J=7.93 Hz, 2H) 4.23-4.32 (m, 1 H) 4.53-4.61 (m, 1H) 7.01 (s, 1H) 7.30 (d, J=8.33 Hz, 1H) 7.51 (dd, J=8.13, 1.39 Hz, 1H) 8.38 (s, 1H); MS (DCI/NH3) m/z 524 (M+H)+.

Workup

  1. customthen quenched with saturated aqueous ammonium chloride
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washwashed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-9fb0e05727ee429db729e42b0dfee6da
Source dataset
uspto-grants-2013_07
Patent number
US08492371B2

Reaction notes

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