Potassium Carbonate → HCID 86677532, compound

HRID 1497902Notes

Reaction equation

HRID 1497902 reaction equation
[OH:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH3:22])=[C:12]([NH:14]C(=O)OC(C)(C)C)[CH:13]=2)[N:4]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.C([O-])([O-])=O.[K+].[K+].[F:43][C:44]1([F:51])[C:47]([F:49])([F:48])[CH2:46][CH:45]1O>ClCCl.O>[CH3:22][C:11]1[CH:10]=[CH:9][C:8]([C:5]2[N:4]=[C:3]([CH2:2][O:1][CH:46]3[CH2:45][C:44]([F:51])([F:43])[C:47]3([F:49])[F:48])[O:7][N:6]=2)=[CH:13][C:12]=1[NH2:14]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 27766212,2,3,3-TetrafluorocyclobutanolHCID 71288128HCID 71288128, compound

Product 1

HCID 86677532HCID 86677532, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
90 °C

Procedure

Tert-butyl (5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamate (137) (0.35 g, 1.15 mmol) was dissovled in dichloromethane (5 mL) and followed by addition of DIEA (0.6 mL, 3.45 mmol) and MsCl (197 mg, 1.72 mmol). The reaction was stirred for 10 minutes. The mixture was diluted with dichloromethane (10 mL) and washed with water. The organic layers were combined, dried over Na2SO4, filtered and concentrated to give a residue which was dissolved in 2,2,3,3-tetrafluorocyclobutanol (2 mL) and followed by addition of K2CO3(476 mg, 3.45 mmol). The reaction mixture was heated at 90° C. for 2-3 hours. The mixture was diluted with water (10 mL) and extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered and concentrated. To this residue was added TFA (1 mL) and stirred for 15 minutes. Then aqueous Na2CO3(2M, 20 mL) was added and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated. Purification by column chromatography on silica gel gave 2-methyl-5-(5-((2,2,3,3-tetrafluorocyclobutoxy)methyl)-1,2,4-oxadiazol-3-yl)aniline (138). 1H NMR (400 MHz, CDCl3) δ 9.36 (bs, 2H), 8.12 (d, J=1.2 Hz, 1H), 7.91 (dd, J=1.2, 8.0 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 4.95 (dd, J=14.4, 68.4 Hz, 2H), 4.51 (m, 1H), 2.95 (m, 1H), 2.51-2.68 (m, 4H). MS m/z 332.0 (M+1)+.

Workup

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue which
  6. extractionextracted with EtOAc
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionTo this residue was added TFA (1 mL)
  11. stirringstirred for 15 minutes
  12. additionThen aqueous Na2CO3(2M, 20 mL) was added
  13. extractionextracted with EtOAc
  14. dry with materialThe organic layers were dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurification by column chromatography on silica gel

Sources & evidence

ORD record
ord-33a2f5b1db5f488b95e9abee72739aa4
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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