Trimethylboroxine → HCID 25010058, compound

HRID 2093232Notes

Reaction equation

HRID 2093232 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C@H:8]2[O:12][C:11](=[O:13])[N:10]([CH2:14][C:15]3[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=3[C:25]3[CH:26]=[C:27]([C:33]4[CH:38]=[CH:37][C:36]([C:39]([O:41][CH3:42])=[O:40])=[CH:35][C:34]=4[CH3:43])[CH:28]=[CH:29][C:30]=3[O:31][CH3:32])[C@H:9]2[CH3:44])[CH:5]=[CH:4][N:3]=1.[CH3:45]B1OB(C)OB(C)O1>C1COCC1.C([O-])([O-])=O.[K+].[K+].O.CCOC(C)=O>[CH3:32][O:31][C:30]1[CH:29]=[CH:28][C:27]([C:33]2[CH:38]=[CH:37][C:36]([C:39]([O:41][CH3:42])=[O:40])=[CH:35][C:34]=2[CH3:43])=[CH:26][C:25]=1[C:16]1[CH:17]=[CH:18][C:19]([C:21]([F:24])([F:23])[F:22])=[CH:20][C:15]=1[CH2:14][N:10]1[C@@H:9]([CH3:44])[C@@H:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:45])[CH:7]=2)[O:12][C:11]1=[O:13]

Participants

7

Reactant 2

HCID 574072TrimethylboroxineHCID 25010057HCID 25010057, compound

Product 1

HCID 25010058HCID 25010058, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 2″-{[(4S,5R)-5-(2-chloropyridin-4-yl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (48 mg, 0.077 mmol) in THF (1 mL) and K2CO3 (1N) (1 mL) was added trimethylboroxine (0.107 mL, 0.768 mmol) and 1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (7.1 mg, 0.011 mmol) The mixture was sealed and heated at 80° C. overnight. The mixture was diluted with water and EtOAc and filtered through Celite. The organic layer was separated and the aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with brine (1×), dried (Na2SO4), filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica gel to give methyl 4′-methoxy-2-methyl-2″-{[(4S,5R)-4-methyl-5-(2-methylpyridin-4-yl)-2-oxo-1,3-oxazolidin-3-yl]methyl}-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. LCMS calc.=605.2; found=605.0 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers) δ 8.49 (t, J=4.3 Hz, 1 H); 7.98 (t, J=6.6 Hz, 1 H); 7.91 (t, J=10.0 Hz, 1 H); 7.73 (s, 0.5 H); 7.67 (s, 0.5 H); 7.65 (s, 1 H); 7.47-7.39 (m, 2 H); 7.33-7.26 (m, 1 H); 7.15 (dd, J=2.2, 5.7 Hz, 1 H); 7.09 (dd, J=6.8, 8.4 Hz, 1 H); 7.06 (s, 0.5 H); 7.00 (s, 0.5 H); 6.95 (d, J=4.8 Hz, 0.5 H); 6.90 (d, J=4.7 Hz, 0.5 H); 5.43 (d, J=8.2 Hz, 0.5 H); 5.18 (d, J=8.1 Hz, 0.5 H); 4.92 (d, J=15.8 Hz, 0.5 H); 4.87 (d, J=15.8 Hz, 0.5 H); 4.22 (d, J=15.8 Hz, 0.5 H); 4.00 (d, J=15.8 Hz, 0.5 H); 3.95 (s, 3 H); 3.89 (s, 1.5 H); 3.88 (s, 1.5 H); 3.81-3.73 (m, 1 H); 2.57 (s, 1.5 H); 2.56 (s, 1.5 H); 2.39 (s, 1.5 H); 2.34 (s, 1.5 H); 0.57 (d, J=6.6 Hz, 1.5 H); 0.47 (d, J=6.6 Hz, 1.5 H).

Workup

  1. customwas sealed
  2. filtrationfiltered through Celite
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine (1×)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-d9e2e1e3ef7d40bdb9a88aa6ea659da4
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

Loading…