Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → 4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one

HRID 1988209Notes

Reaction equation

HRID 1988209 reaction equation
[NH2:1][C:2]1[O:6][C:5]([C:7]([OH:14])([CH2:12][CH3:13])[C:8]([F:11])([F:10])[F:9])=[N:4][N:3]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:31]3[C:26](=[CH:27][C:28]([CH:32]=O)=[CH:29][CH:30]=3)[O:25][C:24](=[O:34])[CH:23]=2)=[CH:18][CH:17]=1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.CCO>[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:31]3[C:26](=[CH:27][C:28]([CH2:32][NH:1][C:2]4[O:6][C:5]([C:7]([OH:14])([C:8]([F:11])([F:9])[F:10])[CH2:12][CH3:13])=[N:4][N:3]=4)=[CH:29][CH:30]=3)[O:25][C:24](=[O:34])[CH:23]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 4311764Sodium borohydrideHCID 468452294-(4-Fluorophenyl)-2-oxo-2H-chromene-7-carbaldehydeHCID 469421982-(5-Amino-1,3,4-oxadiazol-2-yl)-1,1,1-trifluorobutan-2-ol

Product 1

HCID 118561694-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)methyl]-2H-chromen-2-one

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of oxadiazole (14.41 g, 68.2 mmol) of step 3 and 4-(4-fluorophenyl)-2-oxo-2H-chromene-7-carbaldehyde (14.1 g, 52.5 mmol) in toluene (160 mL) with 10% of PPTS was brought to reflux and let go overnight. The system was equipped with a Dean-Stark trap to collect water. The solvent was removed and the crude oil (1H NMR (400 MHz, acetone-d6): δ 9.33 (1H, s, imine)) obtained was diluted in EtOH (ca. 75 mL) at 0° C. To this solution was added NaBH4 (1.9 g) portionwise and the reaction was quenched with a solution of NH4Cl after 45 min. The mixture was saturated with NaCl and extracted with EtOAc (3×200 mL). The organic phases were combined and dried over MgSO4. Purification over silica gel chromatography using toluene-EtOAc (55:45) gave the title compound. 1H NMR (400 MHz, acetone-d6): δ 7.65 (m, 2H), 7.50 (m, 3H), 7.38 (m, 3H), 6.35 (s, 1H), 6.06 (s, 1H), 4.70 (m, 2H), 2.21 (m, 1H), 2.11 (m, 1H) and 0.98 (t, 3H).

Workup

  1. temperatureto reflux
  2. customThe system was equipped with a Dean-Stark trap
  3. customto collect water
  4. customThe solvent was removed
  5. customthe crude oil (1H NMR (400 MHz, acetone-d6): δ 9.33 (1H, s, imine)) obtained
  6. customthe reaction was quenched with a solution of NH4Cl after 45 min
  7. extractionextracted with EtOAc (3×200 mL)
  8. dry with materialdried over MgSO4
  9. customPurification over silica gel chromatography

Sources & evidence

ORD record
ord-2b3f6421009e40dfa6032e548be679e3
Source dataset
uspto-grants-2009_06
Patent number
US07553973B2

Reaction notes

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