Sodium Carbonate → HCID 59118256, compound

HRID 896868Notes

Reaction equation

HRID 896868 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[Cl:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[OH:37][C@H:38]([C:60]1[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=1)[CH2:39][N:40]([CH2:48][C@H:49]1[CH2:58][CH2:57][C:56]2[C:51](=[CH:52][CH:53]=[C:54](I)[CH:55]=2)[O:50]1)C(=O)OC(C)(C)C>C1(C)C=CC=CC=1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:54]2[CH:55]=[C:56]3[C:51](=[CH:52][CH:53]=2)[O:50][C@@H:49]([CH2:48][NH:40][CH2:39][C@@H:38]([C:60]2[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=2)[OH:37])[CH2:58][CH2:57]3)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343303,4-Dichlorobenzeneboronic acidHCID 59118234HCID 59118234, compound

Product 1

HCID 59118256HCID 59118256, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

3,4-Dichlorophenylboronic acid (34 mg, 0.18 mmol), a solution of palladium acetate (3 mg, 0.01 mmol) and triphenylphosphine (12 mg, 0.05 mmol) in toluene (1 mL), and 2 M aqueous sodium carbonate (1 mL) were added successively to a solution of tert-butyl (2R)-2-hydroxy-2-(3-pyridinyl)ethyl{[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}carbamate (Example 37, 60 mg, 0.12 mmol) in toluene (2 mL). The mixture was heated (80° C.) and stirred for 16 hours. After cooling the reaction was diluted with dichloromethane (5 mL) and the layers were separated. The organic layer was concentrated in vacuo and the residue was dissolved in a solution of 4 M hydrogen chloride in dioxane (4 mL). The solution was stirred for 16 hours and then concentrated in vacuo. Preparative reverse phase HPLC of the residue using acetonitrile/water afforded 10.3 mg (20%) of the desired product (retention time=2.19 min.): 1H NMR (CD3OD, δ): 8.71 (d, J=2.2 Hz, 1 H), 8.59 (dd, J=5.1, 1.5 Hz, 1 H), 8.11 (ddd, J=7.9, 1.7, 1.7 Hz, 1 H), 7.71 (d, J=2.3 Hz, 1 H), 7.61 (dd, J=7.9, 5.1 Hz, 1 H), 7.37-7.56 (m, 4 H), 6.99 (d, 9.2 Hz, 1 H), 5.22 (dd, J=10.5, 2.9 Hz, 1 H), 4.43-4.54 (m, 1 H), 3.26-3.55 (m, 4 H), 2.87-3.10 (m, 2 H), 2.11-2.22 (m, 1 H), 1.76-1.92 (m, 1 H); mass spectroscopy gave m/z=429.2 [M+H]+.

Workup

  1. temperatureAfter cooling the reaction
  2. customthe layers were separated
  3. concentrationThe organic layer was concentrated in vacuo
  4. dissolutionthe residue was dissolved in a solution of 4 M hydrogen chloride in dioxane (4 mL)
  5. stirringThe solution was stirred for 16 hours
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-082df2fca3f8412fb479f5e00984af21
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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