Lithium hydroxide, monohydrate → 2-{4-[((3R,5S)-4-{[(1,1-Dimethylethyl)oxy]carbonyl}-3,5-dimethyl-1-piperazinyl)methyl]phenyl}-2-methylpropanoic Acid

HRID 43355Notes

Reaction equation

HRID 43355 reaction equation
[CH3:1][C:2]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]2[CH2:20][C@H:19]([CH3:21])[N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:17]([CH3:29])[CH2:16]2)=[CH:10][CH:9]=1)([CH3:7])[C:3]([O:5]C)=[O:4].O.[OH-].[Li+]>O.O1CCOCC1>[CH3:28][C:25]([O:24][C:22]([N:18]1[C@@H:17]([CH3:29])[CH2:16][N:15]([CH2:14][C:11]2[CH:12]=[CH:13][C:8]([C:2]([CH3:1])([CH3:7])[C:3]([OH:5])=[O:4])=[CH:9][CH:10]=2)[CH2:20][C@H:19]1[CH3:21])=[O:23])([CH3:26])[CH3:27]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 252242061,1-Dimethylethyl (2R,6S)-4-({4-[1,1-dimethyl-2-(methyloxy)-2-oxoethyl]phenyl}methyl)-2,6-dimethyl-1-piperazinecarboxylate

Product 1

HCID 252242082-{4-[((3R,5S)-4-{[(1,1-Dimethylethyl)oxy]carbonyl}-3,5-dimethyl-1-piperazinyl)methyl]phenyl}-2-methylpropanoic AcidYield 82.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of D47 (395 mg, 0.978 mmol) and lithium hydroxide monohydrate (82 mg, 1.95 mmol) in water (5 ml) and 1,4-dioxane (10 ml) was stirred at room temperature for 3 days. The solvents were removed in vacuo and the residue dissolved in water. The solution was washed with ether, acidified to pH4 with 1M HCl then extracted with DCM (×2). The combined organics were dried (Na2SO4) and concentrated in vacuo to give the title compound as a yellow foam (316 mg). δH (CDCl3, 250 MHz) 7.35 (4H, m), 4.11 (2H, br), 3.71 (2H, br), 2.67 (2H, br), 2.17 (2H, br), 1.61 (6H, s), 1.46 (9H, s), 1.33 (6H, br d). MS (ES): MH+ 391, (M−H+) 389.

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutionthe residue dissolved in water
  3. washThe solution was washed with ether
  4. extractionthen extracted with DCM (×2)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-52225b07782d452db6fd71c6a69065ae
Source dataset
uspto-grants-2013_09
Patent number
US08536182B2

Reaction notes

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