Water → HCID 66697276, compound

HRID 2096727Notes

Reaction equation

HRID 2096727 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](OS(C(F)(F)F)(=O)=O)=[CH:4][C:3]=1[CH:16]([CH3:35])[C:17]([OH:34])([C:22]1[CH:23]=[CH:24][C:25]2[O:30][CH2:29][C:28](=[O:31])[N:27]([CH3:32])[C:26]=2[CH:33]=1)[C:18]([F:21])([F:20])[F:19].[C:36]([C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1)([OH:38])=[O:37].O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:42]2[CH:43]=[CH:44][C:39]([C:36]([OH:38])=[O:37])=[CH:40][CH:41]=2)=[CH:4][C:3]=1[CH:16]([CH3:35])[C:17]([OH:34])([C:22]1[CH:23]=[CH:24][C:25]2[O:30][CH2:29][C:28](=[O:31])[N:27]([CH3:32])[C:26]=2[CH:33]=1)[C:18]([F:19])([F:20])[F:21]

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 86645867HCID 86645867, compound

Product 1

HCID 66697276HCID 66697276, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of trifluoromethanesulfonic acid 4-chloro-3-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-propyl]-phenyl ester (100 mg), 4-carboxyphenylboronic acid (48 mg) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]dichloromethane adduct (7.5 mg) in dioxan (0.54 ml) under argon were added water (0.4 ml) and a 2 M aqueous sodium carbonate solution (0.27 ml). The mixture was stirred at 80° C. for 7 h, at 50° C. for 2 days and again at 80° C. for 5 h. The mixture was filtered and to the filtrate was added an aqueous KHSO4 solution. The mixture was extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, CH2Cl2/MeOH 1:0=>85:15) to give the title compound (38 mg) as a light brown solid. MS (m/e, ISP neg. ion)=518.2 [M−H+].

Workup

  1. filtrationThe mixture was filtered and to the filtrate
  2. additionwas added an aqueous KHSO4 solution
  3. extractionThe mixture was extracted with EtOAc
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by chromatography (SiO2, CH2Cl2/MeOH 1:0=>85:15)

Sources & evidence

ORD record
ord-bde4330e957745208e1d7dc8f118f2db
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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