Dabco → HCID 10216146, compound

HRID 2181463Notes

Reaction equation

HRID 2181463 reaction equation
[CH2:1]([C:4]1[CH:25]=[CH:24][C:7]([NH:8][C:9]2[C:21]([F:22])=[C:20]([F:23])[CH:19]=[CH:18][C:10]=2[C:11]([NH:13][O:14][CH2:15][CH2:16][OH:17])=[O:12])=[C:6]([F:26])[CH:5]=1)[CH:2]=C.[C:27]([O-:30])([O-])=O.[K+].[K+].N12CCN(CC1)CC2.[O-:41]S(S([O-])=O)=O.[Na+].[Na+]>C(O)(C)(C)C.O=[Os](=O)(=O)=O.O>[OH:41][CH:2]([CH2:27][OH:30])[CH2:1][C:4]1[CH:25]=[CH:24][C:7]([NH:8][C:9]2[C:21]([F:22])=[C:20]([F:23])[CH:19]=[CH:18][C:10]=2[C:11]([NH:13][O:14][CH2:15][CH2:16][OH:17])=[O:12])=[C:6]([F:26])[CH:5]=1

Participants

9

Reactant 4

HCID 9237DabcoHCID 11430Potassium CarbonateHCID 24489Sodium DithioniteHCID 10193807HCID 10193807, compound

Product 1

HCID 10216146HCID 10216146, compoundYield 64%

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

The product of Example 6, 2-(4-allyl-2-fluoroanilino)-3,4-difluoro-N-(2-hydroxyethoxy)benzamide (227 mg, 0.62 mmol) was dissolved in tert-butanol (15 mL) and water (15 mL) to which was added K2CO3 (257 mg, 1.86 mmol), K3Fe(CN)6 (613 mg, 1.86 mmol) and 1,4-diazabicyclo[2.2.2]octane (70 mg, 0.62 mmol). To this mixture was then added a 4% w/w solution of OsO4 in water (0.21 ml, 0.031 mmol). The reaction was then stirred 15 h. at room temperature, poured into 10% Na2S2O4 (100 mL), and this aqueous solution extracted with EtOAc (3×80 mL). The EtOAc extracts were combined, washed with saturated NaCl solution and dried (Na2SO4), then the solvent removed under reduced pressure to afford a viscous oil. This oil was purified by flash chromatography on silica (10% MeOH/CH2Cl2 as eluant) to give 2-[4-(2,3-dihydroxypropyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide as a cream solid (159 mg, 64%); m.p. (Et2O) 118-120° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.86 (br s, 1 H), 8.78 (br s, 1 H), 7.44-7.37 (m, 1 H), 7.14-7.08 (m, 1 H), 7.05 (dd, J=12.8, 1.7 Hz, 1 H), 6.90 (dd, J=8.2, 1.6 Hz, 1 H), 6.81 (ddd, J=8.8, 8.8, 4.5 Hz, 1 H), 4.71 (br s, 1 H), 4.55 (t, J=6.1 Hz, 2 H), 3.57 (t, J=4.9 Hz, 2 H), 3.63-3.55 (m, 2 H), 3.30-3.20 (m, 2 H), 2.71 (dd, J=13.8, 4.5 Hz, 1 H), 2.43-2.49 (m, 2 H). HRMS (EI+) calcd. For C18H19F3N2O5 400.1246 (M+), found 400.1248. Anal. calcd. for C18H19F3N2O5: C, 54.0; H, 4.8; N, 7.0. Found: C, 54.0; H, 4.8; N, 7.0.

Workup

  1. extractionthis aqueous solution extracted with EtOAc (3×80 mL)
  2. washwashed with saturated NaCl solution
  3. dry with materialdried (Na2SO4)
  4. customthe solvent removed under reduced pressure
  5. customto afford a viscous oil
  6. customThis oil was purified by flash chromatography on silica (10% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-addf90e2621a43828feb7b2d46c7fa72
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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