Metaperiodic acid → (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-morpholinoquinolin-6-yl)acetic acid

HRID 931793Notes

Reaction equation

HRID 931793 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:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)=[C:20]2[C:25](=[CH:26][C:27]=1[CH3:28])[N:24]=[C:23]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[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:35]2[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=2)=[C:20]2[C:25](=[CH:26][C:27]=1[CH3:28])[N:24]=[C:23]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[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 66630867(S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-morpholinoquinolin-6-yl)ethanol

Product 2

HCID 56644640(S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-morpholinoquinolin-6-yl)acetic acidYield 139.7%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)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-morpholinoquinolin-6-yl)ethanol (10 mg) in wet acetonitrile (1.5 mL, 0.75% H2O) at 0° C. The reaction mixture was stirred for 30 minutes at 0° C. Filtration and purification by reverse phase HPLC (0.1% TFA/CH3CN-0.1% TFA/H2O) gave (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-morpholinoquinolin-6-yl)acetic acid (7.2 mg). 1H-NMR 400 MHz, (CD3OD) δ 7.76 (m, 2 H), 7.62 (m, 3 H), 7.30 (m, 2 H), 5.14 (s, 1H), 3.89 (m, 8H), 2.66 (s, 3H), 0.97 (s, 9H); LCMS-ESI+ (m/z): [M+H]+ calcd for C26H30ClN2O4: 469.2. Found: 469.3; LCMS-ESI− (m/z): [M−H]− calcd for C26H28ClN2O4: 467.2 Found: 467.0.

Workup

  1. filtrationFiltration and purification by reverse phase HPLC (0.1% TFA/CH3CN-0.1% TFA/H2O)

Sources & evidence

ORD record
ord-a5ce612be62c4f3d8ef2bc738d905b04
Source dataset
uspto-grants-2016_03
Patent number
US09296758B2

Reaction notes

Loading…