m-Chloroperbenzoic acid → HCID 59085853, compound

HRID 397528Notes

Reaction equation

HRID 397528 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH2:5][C:6]1[C:11]([Cl:12])=[CH:10][N:9]=[C:8]([N:13]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:14][C:15]([F:23])([F:22])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[C:7]=1[F:31])[CH3:2].ClC1C=C(C=CC=1)C(OO)=[O:38]>ClCCCl.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:32])[CH2:5][C:6]1[C:11]([Cl:12])=[CH:10][N:9]=[C:8]([N:13]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:14][C:15]([F:23])([F:22])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N+:17]=2[O-:38])[C:7]=1[F:31])[CH3:2]

Participants

5

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 23000568HCID 23000568, compound

Product 1

HCID 59085853HCID 59085853, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.8 g (1.7 mmol) ethyl(2-{(tert-butoxycarbonyl)[2,2-difluoro-2-(2-pyridinyl)ethyl]amino}-5-chloro-3-fluoro-4-pyridinyl)acetate 1-6 in 3 mL 1,2-dichloroethane was added 0.44 g (1.8 mmol, 70% by weight) m-chloroperoxybenzoic acid. The reaction mixture was stirred at room temperature 16 h, heated to 60° C. 2 h, cooled, diluted with 300 mL EtOAc, washed with 200 mL 0.1M NaOH, and 200 mL brine. Dried over Na2SO4, filtered, and concentrated. Purification by automated flash chromatography (40 g silica cartridge, linear gradient 1-10% MeOH/CH2Cl2 over 25 min, 40 mL/min flow rate) followed by repurification of the mixed fractions by traditional silica gel chromatography (2×15 cm silica gel, linear gradient 2-5% MeOH/CH2Cl2) afforded ethyl(2-{(tert-butoxycarbonyl)[2,2-difluoro-2-(1-oxido-2-pyridinyl)ethyl]amino}-5-chloro-3-fluoro-4-pyridinyl)acetate 1-7. 1H NMR (400 mHz, CDCl3) δ8.20 (s, 1H); 8.18 (br d, 1H, J=5 Hz); 7.57 (br dd, 1H, J=7.7 and 2 Hz); 7.31 (br m, 2H); 5.0 (br m, 2H); 4.19 (q, 2H, J=7.14 Hz); 3.82 (s, 2H); 1.28 (s, 9H); 1.25 (t, 3H, J=7.14 Hz). Mass spectrum (electrospray) M+H=490.1

Workup

  1. temperatureheated to 60° C
  2. temperature2 h, cooled
  3. washwashed with 200 mL 0.1M NaOH, and 200 mL brine
  4. dry with materialDried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by automated flash chromatography (40 g silica cartridge, linear gradient 1-10% MeOH/CH2Cl2 over 25 min, 40 mL/min flow rate)
  8. customfollowed by repurification of the mixed fractions by traditional silica gel chromatography (2×15 cm silica gel, linear gradient 2-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-1e933219b3534cfcae1e86e126019c1d
Source dataset
uspto-grants-2003_08
Patent number
US06610701B2

Reaction notes

Loading…