Water → HCID 66697276, compound

HRID 2386708Notes

Reaction equation

HRID 2386708 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-b0cb3b1c98514b6a831025e12e6d8e21
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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