Methanol → HCID 178448619, compound

HRID 2064504Notes

Reaction equation

HRID 2064504 reaction equation
Br[C:2]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:3]=1[C:4](/[N:6]=[C:7]1/[N:8]([CH2:17][CH2:18][CH2:19][CH3:20])[N:9]([CH3:16])[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:11]/1)=[O:5].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[Br-].[CH2:59]([O:61][C:62](=[O:66])[CH2:63][CH2:64][Zn+])[CH3:60].CO>O1CCCC1.O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[CH2:17]([N:8]1[N:9]([CH3:16])[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:11]/[C:7]/1=[N:6]\[C:4]([C:3]1[CH:21]=[C:22]([C:25]([F:28])([F:27])[F:26])[CH:23]=[CH:24][C:2]=1[CH2:64][CH2:63][C:62]([O:61][CH2:59][CH3:60])=[O:66])=[O:5])[CH2:18][CH2:19][CH3:20]

Participants

10

Reactant 4

HCID 887MethanolHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 178448618HCID 178448618, compoundHCID 178471816HCID 178471816, compound

Product 1

HCID 178448619HCID 178448619, compoundYield 98%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
65 °C

Procedure

To a mixture of Example 11A (400 mg, 0.869 mmol), palladium acetate (19.5 mg, 0.087 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (71.3 mg, 0.174 mmol) was added a solution of (3-ethoxy-3-oxopropyl)zinc(II) bromide (4.17 mL, 2.085 mmol) in tetrahydrofuran. This mixture was heated at 65° C. for 12 hours then cooled to room temperature and diluted with water and ethyl acetate. The organic layer was separated, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, eluted with a gradient of 15-100% hexanes in solvent B, solvent B: 10:1:0.5 ethyl acetate:methanol:triethylamine) to afford the title compound (410 mg, 0.851 mmol, 98% yield). 1H NMR (300 MHz, CDCl3) δ ppm 0.96 (t, J=7.29 Hz, 3H) 1.19-1.23 (m, 3H) 1.37-1.41 (m, 2H) 1.44 (s, 9H) 1.64-1.74 (m, 2H) 2.73-2.78 (m, 2H) 3.40 (t, J=7.46 Hz, 2H) 3.80 (s, 3H) 4.10 (q, J=7.12 Hz, 2 H) 4.25-4.39 (m, 2H) 6.91-7.01 (m, 1H) 7.31-7.33 (m, 1H) 7.48 (dd, J=8.14, 1.36 Hz, 1 H) 8.17 (s, 1H); MS (DCI/NH3) m/z 482 (M+H)+.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography
  7. washeluted with a gradient of 15-100% hexanes in solvent B, solvent B

Sources & evidence

ORD record
ord-488c56fb369142d4aca84541e1a30404
Source dataset
uspto-grants-2012_10
Patent number
US08288428B2

Reaction notes

Loading…