Metaperiodic acid → (S)-2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)acetic acid

HRID 513992Notes

Reaction equation

HRID 513992 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:27]([CH3:28])=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[CH2:16][OH:17])([CH3:13])([CH3:12])[CH3:11]>C(#N)C.O>[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:27]([CH3:28])=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:16]([OH:6])=[O:17])([CH3:13])([CH3:11])[CH3:12]

Participants

7

Reactant 3

HCID 65185Metaperiodic acidHCID 10219390chromium (VI) trioxideHCID 67126174(S)-2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)ethanol

Product 2

HCID 56601710(S)-2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)acetic acidYield 103.7%HCID 131721976Periodic acid chromium trioxide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (0.80 mL) was added to a solution of (S)-2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)ethanol (3J) (51.7 mg, 0.14 mmol) in wet acetonitrile (2.0 mL), 0.75% H2O) at 0° C. The reaction mixture was stirred for 30 minutes at 0° C. and quenched with 1.5 M K2HPO4 solution. Ethyl acetate was added and organic layer separated and washed with 1:1 brine/H2O (2×), then saturated NaHSO3/brine. The organic layer was dried (MgSO4), filtered and concentrated and purified by reverse phase HPLC (Gemini, 50 to 95% ACN/H2O+0.1% TFA) and the product lyophilized to give 3K as a white powder (27.8 mg). 1H-NMR: 300 MHz, (CDCl3) δ 7.73 (d, J=7.8 Hz, 1H), 7.64 (s, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.50-7.38 (m, 3H), 7.28-7.22 (m, 3H), 5.25 (s, 1H), 2.54 (s, 3 H), 0.98 (s, 9H). LCMS-ESI− (m/z): [M−H]− calcd for C23H22ClO3: 381.88. Found: 380.9, 382.9.

Workup

  1. customquenched with 1.5 M K2HPO4 solution
  2. additionEthyl acetate was added
  3. customorganic layer separated
  4. washwashed with 1:1 brine/H2O (2×)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by reverse phase HPLC (Gemini, 50 to 95% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-032f83f50c504807846afdc5fbb3ec7f
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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