Metaperiodic acid → (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-oxo-1,2-dihydroquinolin-6-yl)acetic acid

HRID 931740Notes

Reaction equation

HRID 931740 reaction equation
[I:1]([OH:5])(=[O:4])(=[O:3])=[O:2].[O-2:6].[O-2].[O-2].[Cr+6:9].[C:10]([O:14][C@@H:15]([C:18]1[C:19]([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)=[C:20]2[C:25](=[CH:26][C:27]=1[CH3:28])[NH:24][C:23](=[O:29])[CH:22]=[CH:21]2)[CH2:16][OH:17])([CH3:13])([CH3:12])[CH3:11]>C(#N)C>[I:1]([OH:5])(=[O:4])(=[O:3])=[O:2].[O-2:14].[O-2:6].[O-2:2].[Cr+6:9].[C:10]([O:14][C@@H:15]([C:18]1[C:19]([C:30]2[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=2)=[C:20]2[C:25](=[CH:26][C:27]=1[CH3:28])[NH:24][C:23](=[O:29])[CH:22]=[CH:21]2)[C:16]([OH:6])=[O:17])([CH3:13])([CH3:11])[CH3:12]

Participants

6

Reactant 3

HCID 65185Metaperiodic acidHCID 10219390chromium (VI) trioxideHCID 66633284(S)-6-(1-tert-butoxy-2-hydroxyethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-one

Product 2

HCID 66631789(S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-oxo-1,2-dihydroquinolin-6-yl)acetic acidYield 87.7%HCID 131721976Periodic acid chromium trioxide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

A stock solution of periodic acid/chromium trioxide was prepared according to WO 99/52850 by dissolving periodic acid (11.4 g, 50.0 mmol) and chromium trioxide (23 mg, 1.2 mol %) in wet acetonitrile (0.75% H2O) to a volume of 114 mL. This stock solution (0.40 mL) was added to a solution of (S)-6-(1-tert-butoxy-2-hydroxyethyl)-5-(4-chlorophenyl)-7-methylquinolin-2(1H)-one (8K, 4.4 mg) in wet acetonitrile (1.5 mL, 0.75% H2O) at 0° C. After stirring for 60 min at 0° C., the reaction was quenched with 1.5 M K2HPO4 solution and extracted with ethyl acetate (2×). The combined organic layer was washed with 1:1 brine/H2O (2×), saturated NaHSO3/brine, and was dried (MgSO4). Concentration and purification by prep-HPLC gave (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-oxo-1,2-dihydroquinolin-6-yl)acetic acid (8L) (2 mg). 1H-NMR 300 MHz, (CD3OD) 7.56-7.53 (3H, m), 7.35 (1H, d, J=9.7 Hz), 7.28 (1H, d, J=8.2 Hz), 7.22 (1H, s), 6.43 (1H, d, J=9.8 Hz), 5.06 (1H, s), 2.55 (3H, s), 0.95 (9H, s). LCMS-ESI+ (m/z): [M+H]+ calcd for C22H23ClNO4: 400.9. Found: 400.2; LCMS-ESI− (m/z): [M−H]− calcd for C22H21ClNO4: 398.9. Found: 397.9.

Workup

  1. customthe reaction was quenched with 1.5 M K2HPO4 solution
  2. extractionextracted with ethyl acetate (2×)
  3. washThe combined organic layer was washed with 1:1 brine/H2O (2×), saturated NaHSO3/brine
  4. dry with materialwas dried (MgSO4)
  5. concentrationConcentration and purification

Sources & evidence

ORD record
ord-14ba874332164ae784541d256d12e338
Source dataset
uspto-grants-2016_03
Patent number
US09296758B2

Reaction notes

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