m-Chloroperbenzoic acid → HCID 54674388, compound

HRID 869826Notes

Reaction equation

HRID 869826 reaction equation
[CH:1]1([C@H:7]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[N:13][CH:12]=2)[CH3:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC1C=CC(C(O)=[O:25])=CN=1.C1C=C(Cl)C=C(C(OO)=O)C=1.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[CH:1]1([C@H:7]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[CH:15][C:14]([CH2:17][OH:25])=[N:13][CH:12]=2)[CH3:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 1378606-Methylnicotinic acidHCID 516892Sodium BicarbonateHCID 67997793HCID 67997793, compound

Product 1

HCID 54674388HCID 54674388, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of (R)-N-(1-cyclohexylethyl)-6-methylnicotinamide (2.28 g, 9.3 mmol prepared from the starting 6-methylnicotinic acid) in CHCl3 was added MCPBA (2.24 g, 1.4 eq) and stirred for 2 h at rt. Saturated aqueous NaHCO3 was added and the organics extracted with CH2Cl2, dried over Na2SO4 and concentrated under reduced vacuum. The residue was dissolved in a minimal amount of acetic anhydride and heated to 125° C. for 40 min. The crude mixture was cooled to rt and aqueous NaHCO3 added. The mixture was extracted with EtOAc, dried over Na2SO4, filtered and concentrated under vacuum. The resulting residue was stirred in MeOH (15 mL) and K2CO3 (1 g) for 2 h, concentrated under reduced pressure and partitioned between EtOAc and H2O, Solvent removal and purification by column chromatography (silica gel) using 30-100% EtOAc/hexanes afforded 3.2a as a white solid (920 mg, 38%): 1H-NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.13 (dd, J1=8.0 Hz, J2=2.0 Hz, 1H), 7.36 (d, J=8.0 Hz, 1 H), 5.96 (d, J=8.0 Hz, 1H), 4.84 (s, 2H), 4.15-4.08 (m, 1 H), 1.85-1.04 (m, 14 H)); LC-MS (220 nm), >98%, 263.2 [M+H].

Workup

  1. extractionthe organics extracted with CH2Cl2
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced vacuum
  4. dissolutionThe residue was dissolved in a minimal amount of acetic anhydride
  5. temperatureheated to 125° C. for 40 min
  6. temperatureThe crude mixture was cooled to rt
  7. additionaqueous NaHCO3 added
  8. extractionThe mixture was extracted with EtOAc
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. stirringThe resulting residue was stirred in MeOH (15 mL)
  13. waitK2CO3 (1 g) for 2 h
  14. concentrationconcentrated under reduced pressure
  15. custompartitioned between EtOAc and H2O, Solvent removal and purification by column chromatography (silica gel)

Sources & evidence

ORD record
ord-48be8c874a30460f8b92000b2a316350
Source dataset
uspto-grants-2015_03
Patent number
US08969389B2

Reaction notes

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